Billing pearls (Random)

1.  Never write "benign" positional vertigo, its "paroxysmal" positional vertigo unless you want to be downcoded.

2.  Discharge day codes 99238 for less than 30 minutes, 99239 for more than 30 minutes, document time including spent at nursing station doing prescriptions, need not be continuous.

3.  Critical care codes  99291, 99292 for first hour (minutes 31-74) and each additional 30 minutes, respectively.  Must MANAGE some critical aspect of care and not just consult.  Use different ICD9 code than the attending if you are not primary on case.  Time need not be continuous, and time spent off unit eg. looking at X rays with radiologist counts, unlike floor patients.  Aggregate time with partners if applicable.  This is appropriate for er tpa administration.

4.  Prolonged care codes 99356, 99357 for INPATIENTS for first hour (minutes 31-74 and each additional half hour respectively.  Document reason for prolonged service, submit note to carrier, list start and end clock time required.  Time spent off unit eg radiology does not count, but time spent on unit coordinating care counts.

5.  Prolonged care codes 99354, 99355 are analagous to (4) above except they are for outpatients and Face to face time (start and end clock time) must be documented along with reason. 

6.  Modifier 25 for procedure same day as an E/M service usually EEG and EMG are exempt.

7.  Documentation for high level visit: Indicate chronic illness with severe exacerbation and/or side effects such as MS exacerbation, seizure, Dilantin toxicity (if you are still using Dilantin), risk of Morbidity and mortality (INR high in stroke patient), Abrupt neuro change (TIA, seizure, AMS). 

Must include in note  1) 1 new problem needing additional assessment  or 2) 2 old problems inadequately controlled .  Document at least a three way differential (Alzheimer's v. frontotemporal v. LBD?; or MS v. CIS v. ON due to sarcoid).  Document at least 3 management options (Copaxone, Rebif, Betaseron; steroids; gabapentin: Detrol   or    Aggrenox v. Plavix v Asa, lipitor v. simvastatin; SQ heparin to prevent DVT's).   or iv (parenteral) controlled substances.

New consults need CC, 4 facts for HPI, 1 fact each for PSF (past, family, social history), 10 point ROS (see below), 23 point Neuro SSE (see below). 

8.  Office followup high level requires  CC, 4 facts HPI, med list, social fact, 10 point ROS (may sign and date patient form containing some of these), PLANS (labs, meds, to address problem).   midlevel office visit requires CC, 4 point HPI, mention some PMH or current meds, 2 system ROS, palns to address problem (1-2 chronic problems of moderate degree, or uncertainty re risk or prognosis).  Level 3, low level requires a self limited stable problem eg chronic pain needing E/M, CC, pertinent positives and negatives, and PLANS to address problem.  Most documentation falls out on 3 way differential and plans. 

9.  ROS items to be covered in your office intake sheet come from the list:  constitutional, eyes, ENZT, CV, Respiratory, GI, GU, musculoskeletal, skin and or breast, neurologic, endocrine, hematologic/lymphartic, allergic/immunologic, psychiatric.  May be on a separate sheet patient fills out and checks off if MD signs and dates AND refers to it in office note.  Comprehensive ROS has 10 (TEN) items out of 14.

10.  Neuro single system exam requires 25 bulleted items, need to include 23.  These include one of three CV elements (more may be needed for care but not for documentation). The other 22 that must be included are regular parts of neuro exam.  Mandatory-- any 3 vitals (BP, HR, RR, temp, height, weight, orthostatics), general appearance, Fundoscopic exam, one of 3 cardiovascular elements (carotids, heart auscultation, peripheral vascular system), Memory (orientation, attention, recent and remote memory, language, and fund of information), CN's 2;  3,4,6; 5, 7, 8, 9, 11, 12).  CN's one and ten are not required.  Motor exam includes strength (4 ext), tone (4 ext with note of atrophy or abnormal movements), DTR's 4 ext's including pathologic reflexes, Coordination, Gait and station.  Sensory exam-- need one element of sensation recorded. 

Notes-- must document WHY you can't walk a comatose patient eg. .  Constitutional signs and vital signs can be recorded by staff.  Office needs to have an approved abbreviation list.  Note must be legible.  Templates OK, macros OK, pocket cards with elements available from AAN.

Example of a comprehensive Neuro SSE: Well developed.  120/80, HR 72, RR 16.  fundi OK no bruit.  MS: awake, alert, oriented x 3, dig 6 F, 3/3  objects at 5 minutes, nl naming and vocabulary.  CN. VFF, EOMI, facial sensation and power normal, hears well, palate.tongue midline, SCM normal.  Sens: normal PP.  Motor-- nl tone/bulk/power 4 ext. FNF, gait nl, DTR's 2+ and symmetric throughout, normal.

11,  Couselling and coordination of care may be used instead of documentation.  Counselling involves face to face discussion with patient and/or family re tests, treatments, alternatives, prognosis, education.  Coordination of care may involve interactions with other MD's or providers.  Time is key.  Documentation should state number of minutes spent face to face, that more than half time was spent on counselling and coordination of care, with some general idea of what was done.  No history or exam is needed for documentation.

12.  Be sure to document physician referring name for consults.  Be sure to document MDM in detail. 

sCJD mimics NCSE in ICU patients

Lapergue B et al.  Neurology 2010; 74:1995-1999.

10 patients with sCJD were admitted to neuro ICU with initial misdiagnosis of NCSE.  Mean age 64 +/- 13, with gait ataxis (7),cognitive impairment (5), myoclonus (1), visual (5) or auditory (1) hallucinations and sudden stroke like hemiparesis (2).  Disease duration was 106 days (+/- 30 days).  with EEG's strongly suggesting NCSE ( see article for examples).  EEG's responded to therapy with antiepileptic drugs,  On reexamination, EEG's did not show rhytmic activity, but rather periodic or semiperiodic sharp wave complexes with period of .5-1.0 seconds.  These were attenuated by auditory or painful stimuli.  They also fluctuated with drowsiness.  Importantly, there was no clinical improvement with EEG improvement.  MRI showed characteristic changes in 9/10 and 14,3,3 was seen in all patients. 

List: Most common 7 organisms in bacterial meningitis

Streptococcus pneumoniae
Neisseria meningitided
Listeria monocytogenes
Staphylococcus aureus
Haemophilus influenza
Escheria coli
Streptococcus agalactiae

source Lin AL, Safdieh JE.  The Evaluation and Management of bacterial meningitis: current practice and emerging developments.  The Neurologist 2010: 16:143-151.

The Heidenhain variant of Creutzfeldt-Jakob disease

From Neurology resident/fellow page
The Heidenhain variant of Creutzfeldt-Jakob disease


The Heidenhain variant of Creutzfeldt-Jakob disease presents with isolated visual

symptoms for 2-4 weeks, and these may include disturbed perception of colors or shapes,

visual hallucinations, or cortical blindness with anosognosia (Anton syndrome). The

clinical course of this variant is rapidly progressive. Diagnosis is difficult in the early

stage since the neurological examination is otherwise normal and typical EEG findings

are absent. Visual symptoms may be erroneously attributed to ophthalmologic disease,

which in some cases lead to needless ocular procedures. This is particularly important

since prion particles can be transmitted by ocular tissue. Brain MRI may show the

characteristic cortical ribbon sign with diffusion restriction in the parieto-occipital cortex.

CAPS : A treatable neurologic disorder

Kitley JL, et al. Neurology 2010; 74: 1267-1270
Cryopyrin associated periodic disorder (CAPS) is a  rare disorder that, untreated, will progress to amyloidosis, renal failure and death.  It responds dramatically to anti interleukin 1 therapy with cankinumab.  Authors summarize 13 published cases of CAPS neurologic features, including one case of their own and twelve of the literature. 

Highlights
-- includes 3 previously thought to be unrelated conditions, which are the Muckle Wells syndrome, familial cold autoinflammatory syndrome (FCAS), and chronic infantile neurologic, cutaneous and articular syndrome (CINCA). 

Presentation of  adult patients with CAPS included
-- Headache in 12/13; migraine like in 10
-- myalgia in 9
-- hearing impairment in 7
-- papilledema in 6
--optic pallor in 2

MRIs were normal
CSF in 1 patient showed high OP and pleocytosis
FCAS presents with fever, rash, and conjunctivitis provoked by cold; is mildest
MWS is more severe with progressive SN deafness, one third developing amyloidosis, nephrotic syndrome and renal failure
CINCA presents in infancy and is most severe
Some have history of aseptic meningitis

All show episodic fever, urticarial like rash, conjunctivitis, flu like symptoms, acute phase response with anemia, high ESR and CRP, and elevated serum amyloid A.

Nosocomial bacterial meningitis pearls

Van de Beek et al.  NEJM 2010; 362: 146-154.  Current Concepts.  Review article.


1.  Post craniotomy, one third of cases occur in first week, one third in second week, and one third after second week, up to "years" after craniotomy.  The incidence is 0.8-1.5 %.


2.  Internal ventricular catheter infection causes infection 4-17 % of time.  Colonization at time of surgery is the most important cause, and most cases occur within one month.


3.  External ventricular catheter shunts has an 8 % incidence of infection with a sharp rise after five days.  Article suggests no reason to remove a catheter just because 5 days has elapsed.


4.  CHT usually has a basilar skull fracture if infections occur.  This is most common cause of recurrent meningitis.


5.  Gram staining and culture are hallmarks of diagnosis and measurement of cells and diff may be falsely negative in many cases. especially ventricular catheters.


6.  Post neurosurgery, a CSF lactate level of > 4 mmol/L has a sensitivity of 88 %, specificity of 98 %, PPV of 96 %, and a NPV of 94 % for bacterial meningitis.  However, one review suggested many cases would be missed with this cutoff.


7.  Antibiotics postop or post head injury should be vancomycin plus ceftazidine, cefepime, or meropenem.  Goal should be serum trough of 15-20 for vancomycin.  In intraventricular therapy, close the drain for an hour after the first dose.  The trough should equal ten times the MIC of the antibiotic to sterilize the CSF. 

8.  External lumbar catheter infection rates have been reported between .8 and 5 percent.  After LP infection rate is one in 50,000 with 80 cases per year in US. 

9.  Acinteobacter is more common in nosocomial infections that may be resistant.  Initially may use iv meropenem, with or without intrathecal or intraventricular aminoglycoside, if resistant use colistin or polymyxin B.  Colistin in one study sterilized 13/14 patients and cured those.  In another study, all patients treated with colistin survived.

Pharmacology minutiae of antiepileptic drugs

from E Ramsey at AAN

1.  Enzyme induding drugs (Phenytoin, carbamazepine and lamotrigine) cause eighty percent or more reduction of many drugs including statins, (except one), so need to way increase dose of statin. Ditto for calcium channel blockers (think nimodipine after SAH),  antidepressants, erectile dysfunction drugs (all of them), and HAART therapy.

2.  Carbamazepine is related to weight gain almost as much as valproate

3.  Topiramate helps blood pressure and insulin sensitization needing readjustment of insulin

4.  Dilantin will not be absorbed with high pH such as pepcid or protonix

5.  LTG or TOP levels will increase two or three fold if you wean off an inducer like PTN due to decreased clearance

6.   Warfarin metabolism with Dilantin is variable, up or down, depending on genetics.

7.  Drugs that lower seizure threshold include theophylline, antihistamines, stimulants, antipsychotics, narcotics, hormones, antibiotics (PCN, metronidazole, lindane), antidepressants (SSRI, TCA's), baclofen, oral hypoglycemics, some immunosuppressants

8.  CBZ induces CYP34, and ethinyl estradiol is a substrate, hence lower bc pill levels.  

Saline bullets (and hypertonic saline) for increased intracranial pressure.

Saline bullets are not FDA approved but rather a novel effective way to lower increased intracranial pressure acutely.  The idea was proposed by Geoffrey Ling MD at a lecture based on his experience in the military.  The advantage is that hypertonic saline, in this case a saline bullet, does not promote diuresis just creates a gradient that treats increased ICP.  Per Dr. Ling, a saline bullet of 23 % NaCL, 30 cc, decreases ICP by 50 % and sustains the decrease for about eight hours.  It needs to be given through a central line.  The 23 percent saline infusion is available in every pharmacy as a basis for TPN and needs to be cannibalized from that cart since not likely to be available from pharmacy for stated purpose of controlling ICP.  Once the goal is achieved Ling uses a 3 percent saline infusion at 75 cc per hour, of half NaCl and half Naacetate

Pearls CSF and alternate forms of meningitis: PCR for TB, CMV,enterovirus, VZV, toxo meningitis

HSVE
1.  In CSF , PCR has sens/spec of 98 and 94 % respectively, and stay positive for a long time in one third.
2. In cases of false negative, treat with acyclovir anyway for ten days if clinical suspicion is high and consider repeating LP at 48 hours.

CMV
1.   PCR is 79 % sensitive, 95 % specific

toxo
1  PCR in CSF is 42 % sensitive, 100 % specific

enterovirus
1.  more sensitive than viral culture

mycoplasma pn
1.need to check IgM and IgM is CSF: serum

HSVE
1.  Antibody is positive at tn days in half
Tests:
immunocompetent-- initially test with PCR for HSVE, VZV, and enterovirus
immunocompromised -- add  EBV and CMV PCR and HHV6 and HHV7
Consider quantitative CSF: blood esp HIV patients

TB meningitis diagnostic test pearls

H/t Wendy Ziai and John Lewin Neurol Cl May 2008

1. CXR and ppd may be negative in half of cases, and typical  CSF profile may not be present especially in immunosuppressed patients. 

2. AFB in CSF is positive in only 30 % (maybe able to increase to 70 % with meticulous and repeated sampling), culture is only positive in 40-70 %, and may require weeks to have a result.

3.  CSF adenosine deaminase (ADA) activity is a biochemical marker that may help.  At a cutof of 6.97 iu/L it is fairly sensitive and specific  (85 % and 88 % respectively).  ADA is useful in third world countries and poorly equipped labs  (Gautam et al., Nepal Med Coll, 2007). 

4.  Molecular  nucleic acid amplification kits   have sensitivity 60-83 % and specificity of 98 % and should be first line to rule out (Dinnes et al. Health Care Tech  2007)

5. PCR is fastest and most sensitive tests but is not good enough to rule out TB meningitis.

6.  Measurement of interferon gamma  in CSF compared with PCR is more sensitive (70 v 65 %) and has specificity of 94 %.  Interferon gamma plus PCR has 80 % sensitivity.

7.  In general careful bacti is as good as molecular in initially diagnosing TB meningitis although molecular stays positive longer with treatment.

8.  TB is prevalent in indigent urban nonwhite populations with a high rate of HIV infection (Arch Int Med 1996).  Presentation is fever, malaise, headache and personality changes, leading in 2-3 weeks to classic signs such as headache, meningismus, vomting, confusion and focal neurologic findings.  Occassionally it presents like acute bacterial infefctions.

9. MRI classic triad for TB meningitis is basal meningeal enhancement, hydrocephalus, and supratentorial and brainstem infarctions; hydrocephalus can be communicating or noncommunicating.

10.  Outcome scoring system is called Weisfelt system and is calculated one hour after admission based on six variables: age, heart rate, GCS, cranial neuropathies, CSF WBC, Gram stain findings.

Ventriculitis pearls and a few more meningitis pearls

Ventriculitis
1.  Occurs in 30 % of adult meningitis cases, 90  % of neonatal cases.  Often thought of as a late occurrence in refractory meningitis but can occur as primary event also.

2.  Commonly occurs with EVD or VP shunt, less commonly if EVD management protocols are strictly adhered to.

3.  Hemorrhagic CSF is considered a risk factor

4.  Gram positive organisms such as Staph aureus and Staph epidermidis are most common, but gram negative organisms also occur.  (E coli, Klebsiella, Acinetobacter, pseudomonas species.

5.  Cell index is ratio of WBC: RBC in CSF:Serum.  Its used in ventriculostomy cases with IVH to consider infection.  It is one normally and in ventriculitis patients without infection.  In 7 patients with definite ventriculitis, index rose 3 days before diagnosis of ventriculitis and declined with antibiotic treatment (Pfauler et al. Acta Neurchir 2004)

CSF in meningitis
5.  Common practice is to perform CT first, then LP, then begin therapy.  These practices lead to delay in antimicrobial treatment which actually is worse for patient than risk of performing lumbar puncture.  In many cases antibiotics should be given before CT because even a delay of a few hours can be catastrophic.   Aronin et al. ANn Int Med 1998.

6.  Delay of LP is not needed if the following factors are not present:  immunosuppression, ( to R/O toxo or lymphoma), alteration in mentation, focal deficits, seizures, pappilledema, ocular palsies, bradycardia or irregular respirations, sedation or muscle paralysis.   see Mellor DH. Arch Dis Children 1992.

7.  CSF findings in bacterial meningitis WBC> 1000 (60 %) and > 100 (90%); CSF glc < 40 (50 %) but CSF : serum glc < 0.4 80 % sensitive and 98 % specific. 

8.  Blood cultures are positive in about 50 % of cases of bacterial meningitis, but touch preparation of the rash is positive in 70 % on Gram stain.

9.  CSF lactate is not helpful in community acquired meningitis but is helpful in postop neurosurgical cases.  A cutoff of 4 mmol/L lactate in CSF is superior to measuring the glucose CSF: serum ratio.  88 % sensitive, 98 % specific, ppv 96 %, npv 94 %.

10.  Latex agglutination CIE is useful only for certain organisms and in patients with pretreatment of antibiotics and negative cultures.

11.  C reactive protein is sensitive for bacterial meningitis in some pediatric population esp. with CSF profile c/w meningitis but negative gram stain. 

12.  Procalcitonin levels differentiate bacterial and virla meningitis in kids (cutoff > 5, 94 %  sensitive, 100 % specific).  Also in adults ( cutoff > .2 ng/mL , sensitivity and specificity 99 %) .  Moreover the levels decline rapidly, within 24 hours, and may be useful to monitor the effectiveness of the treatment.   (Gendrel et al, Clin Inf Dis 1997, Viallon et al, Clin Inf Dis 1999, ibid. Crit Care 2005).  PCT levels remain normal in ventriculitis and do not help in that situation.

13.  Real time PCR is emerging but disadvantage include a lack of sensitivity, lack of sensitivity to antibiotics result, false negatives and contamination issues.

Infratentorial abscess after bacterial meningitis

Presents with a subacute meningitis and and neck stiffness and decreased consciousness.  It occurs after surgery for otitis, mastoiditis, and sinusitis.  Delay in detection occurs due to CT missing the diagnosis, leading to a high mortality.  MRI with DWI can differentiate this condition from reactive subdural effusion,  which is important due to the risk of hydrocephalus, the need for antibiotics and sometimes surgery (should have low threshold to explore). 
See van de Beek, et al.  Neurology 2007, and Wong et al., AJNR 2004. 

Neurocritical infection/ meningitis pearls

1.  Bacterial meningitis damage is half mediated by toxins, half by inflammatory response

2.  Classic triad of headache, fever, and neck stiffness is NOT sensitive for meningitis.  However, 90 + % of patients have 2 of the following four symptoms:  ha, neck stiffness, fever and mental status changes.14 % of patients are comatose on admission, and 34 % have focal deficits. Only 30 % have nuchal rigidity. Fever is often missing in elderly, immunosuppressed and the partly treated groups.  Overall fever is present in 71-77 % of cases, neck stiffness in 48 %, headache in 87-92 %, nausea and vomiting in 74 %, photophobia 57 %, seizures 5-23 %, focal signs <30 %, rash 11 %.  (see van de Beck, NEJM 2006:354:44-53; Durand NEJM 1993; 321:21-28; Thomas et al, Clin Inf Dis 2002; 35:46-52).  Latter article reveals Kernig's and Brudzinski's signs are NOT reliable and have a positive predictive value in the 20s and sensitivity of less than 10 percent.  Older patients >60 in Dutch study had less fever and neck stiffness and more encephalopathy as a presenting sign. 

In infants, signs can be subtle, bulging fontanelle and seizures is not sensitive (Klein, Pediatrics, 1986), and an LP is warranted(?controversial) in patients with first simple febrile seizure. The presentation is usually fever, lethargy, irritability, respiratory distress, jaundice, reduced food intake, vomiting and diarrhea. 

Immunocompromised patients have the triad only 21 % of time, due to less immune response and greater propensity to get atypical organisms. 

3.  Predictors of bacterial v. viral meningitis include one of the following indicators of severity:  altered consciousness, focal deficits, seizures, and shock.  Non predictors include CSF glc< 2, CSF protein > 2 (Brivet et al, Intensive Care Med 2005).

4.  Predictors of mortality include seizures (34 v. 7 %)  and decreased level of consciousness on admission (26 v. 2 %). 

5.  An unusual presentation of brainstem HSVE in an immunocompromised patient included diplopia, dysarthria, and ataxia .

6.  HSVE also causes radiculitis in immunocompromised (lumbosacral) and most cases of recurrent meningitis (previously called Mollaret's meningitis).
 
7.  WNV in CNS includes movement disorders with myoclonus, postural tremor and cerebellar signs in addition to polio like features.  Death can occur due to respiratory depression.

8.  Presentation of cerebral abscess includes neck stiffness only in 20 % often only shows increased ICP.  Seizures occur in up to 40 %.  Focal specific symptoms such as aphasia occur but are variable.

9. Cranial epidural abscess presents with ha, fever, nausea and usually does not lead to neurologic complications due to neurosurgery>meningitis, with organisms often Strep, Staph and polymicrobial

10.  Subdural empyema occurscausing altered level of consciousness, fever, seizures, septomthrombophlebitis, venous infarcts and more complicated course.  Sources include paranasal sinuses, hematogenous spread due to emissary veins in subdural space, and postoperative extension due to epidural abscess.

11. Peripheral lab clues:  amylase increased in mumps, cold agglutination titers in mycoplasma, CXR  abnormal could be associated with mycoplasma, legionella or lymphocytic chorionic meningitis.

12. Cancer patients much less commonly have the triad (56 % fever, 47 % headaches, 35 % altered mental status, 14 % nuchal rigidity, 14 % completely asymptomatic, and may be related to frequency of a range of neurosurgical procedures (Safdieh, Neurology 2008).


13. Novel lab tests to help diagnose bacterial meningitis include: CSF lactate> 4.2 (nonspecific and only sensitive in acute setting), CRP (normal level has high negative predictive value) and serum procalcitonin level (newest marker) (see Tunkel Clin Inf Dis 2004; Sormunen, J Ped 1999; Viallon et al, Clin Inf Dis 1999 and others).

14. Third generation cephalosporins sterilize the CSF within 2 hours in all patients; in one third by one hour. Latex agglutination and PCR techniques are useful in these situations.

Blast TBI and other TBI pearls

1.  Battlefield injury without breach of cranium thought to have different pathology than standard CHT or penetrating injury.  Its due to a concussive pressure wave. 

2.  Battle armor and helmets, and medical care on the scene have reduced the kill wounded ration to less than 1:10, v 1:4 in WWII. 

3.  Secondary injury factors are the focus of treatment. 

4.  Mild , moderate and severe TBI is defined by GCS.  Mild is 13 or above, moderate is 8-13, and severe is < 8.

5.  Second impact syndrome has a high mortality, up to 50 % but the mechanism is not well understood

6.  Early mgmt recommendations include avoiding hypotension and hypooxygenation in addition to ABC. 

7. The role of hemicraniectomy is being studied in the RESCUE trial

8.  Indications for ICP monitoring include abnormal CT scan, hypotension (SBP < 90), or age > 40.

9.  Hypertonic saline boluses may be as effective as mannitol.  Give through a central line.  2-3 % hypertonic saline through a peripheral line is given half NACL, half Na acetate. 

10. Pseudoaneurysms and vasospasm are very common.

status epilepticus pearls

1,  Among patients with convulsive SE that stops, 14 % have ongoing  subclinical status and 48 % have ongoing intermittent seizures (DeLorenzo et al., Epilepsia 1998)

2.  Risk factors for increased mortality in SE include higher age, intubated, length of time till treated

3.  Fever contributes to cerebellar injury, and neuromuscular blockade prevents (Meldrum 1973 Arch Neurol)

4.  Among eleven patients with SE who died acutely, 8 had contraction band necrosis of cardiac muscle, and died due to initial catechol release Manno et al. Ann Neurol 2005)

5.  Neuron specific enolase (NSE) is unvestigated as a marker for neuronal injury in prolonged SE

6.  The VA cooperative study (Treiman et al, NEJM, 1998) looked at overt status and found the efficacy of each of the following regimens in stopping SE:  lorazepam, 65 %, phenobarbital 58 %, diazepam plus phenytoin, 56 % ,and phenytoin alone 44 %.  Subjects who failed the first drug responded to the second drug (7 %) and the third drug (2.3 %) at a low rate.  The only significant difference statistically was between lorazepam and phenytoin.

7.  Inttravenous valproate may be as good or better than phenytoin or fos-phenytoin ( Aggarwal et al, Seizure, 2007) both as a first line and second line agent (Misra Neurology 2006). If used with phenytoin, it may increase the free level of the drug, paradoxically causing increased seizure.  Antibiotics such as merepenem and amikacin may cause a dramatic fall off in the blood level of valproate, possibly due to increased renal excretion.  Beware of other p450 metabolized medications.  Valproate is a broad spectrum antiepileptic drug, with action against all seizure types including postanoxic myoclonus, and does not sedate or cause hypotension.  Therefore it may be DOC in patients with a DNR order.  Dose is 25 mg.kg

8.  Initial dose of thiopental in ICU setting is 2-4 mg/kg bolus, then 3-5 mg/kg/hour. Pentobarb has slower onset and offset than thiopental and should be dosed initially at 5 mg/kg with repeated boluses of same until seizures stop, with initial maintenance at 25-50 mg/minute, titrated to burst suppression.  Half life is over 34 hours.  Midazolam initial dose is .2 mg/kg, repeated every five minutes up to 2 mg/kg until seizures stop, with a continuous dose range of 0.05 - 2.9 mg/kg/hour. 

9. Propofol has rapid onset and rapid clearing.  Dose is bolus of 1-2 mg/kg,  then a continuous infusion of 1-15 mg/kg/hr with a maximum dose of 5 mg/kg/hr if maintained for days. Beware of "propofol infusion syndrome" of metabolic acidosis, cardiac failure, rhabdomyolysis, hypotension, and death.Risk factors are prolonged doses (> 48 hours), high doses (>5 mg/kg/hr), head injury, lean body mass, and concurrent use of catechols or steroids.  Concurrent clonazepam may also help prevent PIS (Rosetti et al, Epilepsia 2004).

10.  Intravenous levitiracetam is useful in benzo refractory partial seizures, usually stopping it  without causing severe AE's (Knake et al. JNNP 2008).

11.  Ellis looked at patients with grade 3 or 4 hepatic encephalopathy, and found of 42 total patients split between prophylactic AED and controls, subclinical status was common among the control group (45 %) but not in the treated group with    (15 %).  At autopsy the control group had more brain edema (Ellis et al, Hepatology 2000).  This constitutes an argument for continuous EEG monitoring.

12.  In renal patients, AED's are divided into the dialyzable and the nondialyzable.  Highly bound drugs (PTN, VPA, CBZ) are not dialyzed significantly.  Moderate protein binding eg LTG (lamotrigine) may need pre and post dialysis levels.  AED's THAT REQUIRE REPLACEMENT AFTER DIALYSIS ARE GBN, PREGABALIN, ETHOSUXIMIDE, LEVITIRACETAM, PHENOBARBITAL AND TOPIRIMATE. The serum concentrations of these can decrease 50 % after dialysis

13.  Among posttransplant patients, many seizures occur, and many are nonconvulsive. In liver transplant, the incidence may be as high as one third, slightly less in pancreatic, much less with other organs.  Day 4-6 post transplant is highest occurrence.  Most patients do not have prior seizures.  Short term AED's are indicated.

Medications that reduce seizure threshold

from Neurologic Clinics 2008

Antidepressants esp. buproprion and maprotilene
antipsychotics especially phenothiazines and clozapine
Lithium
baclofen
AED withdrawal
super high phenytoin levels
theophylline
Analgesics esp. meperidine-demerol, fentanyl and tramadol
opiod withdrawal
benzodiazepine withdrawal
barbiturate withdrawal
antibiotics-- beta lactams (cefezolin), carbapenems (imipenem), quinolones, isoniazid (treat with B6), metronidazole
antiarythmics-- lidocaine, digoxin, mexelitine
radiographic contrast dyes
immunomodulators-- cyclosporine, tacrolimus, interferons
chemotherapeutic drugs-- alkylating agents such as chlorambucil and busulfan
an

Concussion pearls

1.  See prior posts on sideline assessment and Vienna return to work
2.  Younger athletes (high school) take longer to recover from concussions than college or NFL players on neuropsychologic testing and should be kept out longer accordingly.
3.  the role of multiple concussions in a single season or time between concussions is unclear but under investigation
4.  Clinical head injury in football is strongly related to translational forces.  Rotational forces follow translational forces.  These forces are highest with helmet to helmet hits and backward falls onto ground
5.  Head down strike increases the mass of the striking player 67 % due to alignment of the torso, and thereby increases the severity of concussion accordingly.
6.  Thicker larger and lighter helmets improve the function of prevention and decrease concussion severity
7.  Clinically differentiate early (temporal) injury involving dizziness and later (>40 msec) injuyr involving fornix and midbrain that is more likely associated with memory loss.
8.  The notion of grading concussion the day of the injury may be in error as late cognitive changes are far more important in predicting delayed recovery

Concussion: University of Pittsburgh sideline mental status examination card

Orientation questions
        What stadium is this?
         What city is this?
         Who is opposing team ?
          What month is it?
           What day is it?

Post-traumatic amnesia
            Remember three words:  girl , dog and green (ask player to repeat them)

Retrograde amnesia
           Ask "What happened in prior half"
           "What happened before you were hit"
          "What was the score before the hit"
          "Do you remember the hit"

Concentration
          ask the player to say the days of the week backwards, starting from today
          ask the player to say the following numbers backwards:  63, 419

Memory
          ask the player to recall the three words given earlier


Vienna conference return to play recommendations1.   Remove from game if any signs of concussion- any items missed on sideline exam
2.   No return to play in current game
3.   Medical evaluation after injury   a. rule out serious focal injury     b. neuropsychologic evaluation
4.   Stepwise return to play    a.  rest till asymptomatic      b.   light aerobic      c.  sport specific training     d.  noncontact practice      e. full contact practice     f. return to play

Concussion- player complaint and observer notation

from Mark Lovell  University of Pittsburgh signs and symptoms of concussion

Signs observed by staff                          player complaint

Appears dazed or stunned                     headache

Is confused about assignment                 nausea

Forgets plays                                         balance problem or dizziness

Unsure of game/score opponent             double or fuzzy/blurry vision

Moves clumsily                                      sensitive to light or noise

answers questions slowly                       sluggish/slowed down

loses consciousness                                "foggy" or "groggy"

behavior/personality change                    concentration or memory problem

retrograde amnesia                                  later sleep problem

anterograde amnesia                                fatigue

orbital pseudotumor due to thyroid opthalmopathy v, myositis

Differential points:  left image, from internet, shows medial rectus hypertrophy which (along with inferior rectus) is characteristic of thyroidopthalmopathy.  This condition is also tendon sparing.  Right image is orbital pseudotumor which in this case affects lateral rectus and tendon.  The condition on right can be secondary to a number of different conditions including RA, orbital tumor, Crohn's disease, and others. 

AAN quick hits 2010 novel uses of medication

pseudoatrophy MRI in MS helped with lamotrigine


cerebellar ataxia benefitted with varenicycline


frataxin level in FA helped with single dose erythropoetin




cell death in SCA type 3 (Machado-Joseph disease) helped by Lithium


improved ataxia and tremulousness with levodopa treatment for Angelman's disease

improved hypoxic damage with SSRI's in medically refractory partial epilepsy

CIS conversion to CDMS reduced by atorvastatin 80 mg

SUNCT/SUNA response to occipital nerve stimulator

CLIPPERS syndrome

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids.  Clippers.  (Mayo Clinic) AAN 2010 P02:182.  Eight patients had a distinctive clinical and radiological CNS disease with treatment.  Presentation was episodic diplopia or facial paresthesias with subsequent progressive ataxia, diplopia, dysarthria and paresis responsive to high dose steroids.  MRi showed gado enhanced peppering of pons extending into the medulla.  Weaning steroids always led to worsening.  Neuropath showed perivascular T lymphocytic infiltration without evidence of granulomas, lymphoma or vasculitis. 

2 type disproportionate anterocollis in Parkinson syndromes

Neurology 2020 AAN PO1.274  Clinical subtypes of disproportionate anterocollis in parkinsonian syndromes Revuelta G, Factor S. 


Myopathic subtype-- neck extensor weakness and limited range of motion, neck extensor myopathy on EMG,


dystonic subtype-- no weakness, full range of motion, laterocollis/torticollis and hypertrophy. 

Other Mitochondria disease: MNGIE

MNGIE-  aut rec, presents with abdominal pain, malabsorption and weight loss.  Peripheral neuropathy and leukodystrophy occur.Serum lactate is almost invariably high.  Elevated thymidine is seen, and WBC shows decreased thymidine phosphorylase (buffy coat??).

Clinical presentations of mitochondrial cytopathies MELAS , MERRF and LHON

Melas- hypoacusis, ataxia, dementia, opthalmoplegia, encephalopathy, stroke like syndromes, exercise intolerance, proximal myopathy, type 2 diabetes.  Due to point mutation, can occur at most ages and mimic multiplle sclerosis with progressive or remitting and relapsing presentations

MERRF  isolated myoclonic epilepsy with or without ataxia, myopathy, peripheral neuropathy, and multiple lipomas in head region.  Neuropsychiatric manifestations including OCD, depression, psychosis and type two diabetes are common.  Any age of presentation to mid 40s.  Progressive decline

LHON-  painless, rapidly progressive vision loss with centrocecal scotoma in teenagers or young adults with male predominance (65-35).  Can mimic MS.

Mitchondrial cytopathies

visit http://www.mitomap.org/ for detailed information on cytopathies

Leigh disease (Complex 1>complex 2,3) aut rec
Succinate dehydrogenase gene (SDHB c and D) paraganglioma and pheochromocytoma, aut dom
polymerase gamma (POLG) mutations-- Alpers syndrome (hepatoencephalomyopathy), CPEO, spinocerebellar ataxia, sensory ataxia neuropathy with dysarthria and opthalmoplegia (SANDO),
ECGF1 (thymidine phosphorylase)- MNGIE

GI differential
liver involvement- Alpers syndrome
irritable bowel, intestinal pseudoobstruction--MELAS
severe GI dysfunction--MNGIE

Neuropathy-- MNGIE, SANDO

Historical points to ask about: deafness, short stature, early cardiac death in family, muscle discomfort or exercise intolerance, early onset DM.
Barth syndrome-- deafness and dystonia

Diagnostic tests
elevated lactate-- 60 percent sensitive, not completely specific
lactate/pyruvate ratio in CSF- may differentiate pyruvate dehydrogenase deficiency from primary mit. cytopathy
plasma amino acids-  elevated alanine may be seen
elevated CPK- may be seen in myopathy, not specific
alpha feto protein- may be seen in Alpers' syndrome early along with increased GGTPand others
thymidine levels-- high in MNGIE
urine organic acids-- high levels of ethylmalonic acid prompts ETHE1 gene for encephalopathy
     high 3 methyl glutaconic acid prompts look for tafazzin mutation for Barth syndrome
folate, B12, vitamin E- may be low in percentage coincidentally or secondarily

MRI- high T2 signal in putamen leading to striatal necrosis characterizes Leigh disease
occipital stroke-- consider MELAS

Cerebral palsy for adult neurologists: pearls

1.  Gross Motor Functional Classification System is most widely used

Level I  Ambulatory in all settings
Level II Walks without aids but has limitations in community settings
Level III Walks with aids
Level IV  Requires wheelchair or adult assistance
Level V  Fully dependent for mobility

Of all CP patients, 40 % are level I, and 66 % are levels 1-3 (ie. ambulatory)

2.  O CP patients, approximately one third will have spastic quadriplegia, one third spastic hemiplegia, one fifth spastic diplegia, and the rest either dyskinetic or ataxic-hypotonic CP.  It is rare for CP patients with spastic hemiplegia or spastic diplegia to be nonambulatory, but 75% of spastic quadriplegia patients are not ambulatory.  Those same patients are much more likely to suffer comorbidities such as epilepsy. 

3.  Genetic defects such as DCX and LISI can be sought, and coagulation pathway abnormalities (Leiden mutation eg.) among those suffering from placental thrombosis.

Care of hydrocephalus in adults pearls

1. Hydrocephalus may be decreasing.  Reasons may include higher threshold for surgery (artefact of practice) increased folate in pregnancy causing less myelomeningocoele.

2.  Unchanged CT scan does not exclude obstruction

3.  ETV or endoscopic third ventriculostomy is a more recent alternative to shunting in a highly select group of patients.  The procedure is more prone to immediate catastrophe, but less to long term infection, although obstruction can occur years later (as it can with any shunting procedure).  ETV may be best for older children with obstructive hydrocephalus or aqueductal stenosis.

4.  A top down approach to assessing meningocoele would sequentially assess hydrocephalus, Chiari malformation, syringobulbia.syringomyelia, tethered cord.

Diagnostic criteria for FXTAS (fragile x associated tremor ataxia syndrome)

Molecular-- CGG repeat 55-200
Clinical
   Major intention tremor, cerebellar ataxia
   Minor  Parkinsonism, moderate to severe short term memory loss, executive function deficit
Radiologic
   Major white matter lesions in middle cerebellar peduncles (MCP sign)
   Minor  lesions in cerebral white matter, moderate to severe brain atrophy

Diagnostic categories

Definite-- one major clinical, and one major radiologic, or present inclusions at autopsy
Probable-- two major clinical, or one minor clinical and one major radiologic
Possible-- one major clinical and one minor radiologic

Dystrophinopathies in adults: pearls

See also http://emgnotes.blogspot.com/2010/01/dystrophinopathy-clinical-diagnostic.html and here are ten more pearls

1.  Many DMD patients now live into 30s and 40s as do carriers or those with BMD.  DMD frequency is about 1:3500 whereas BMD is 1:15,000 to 1:35,000.

2.  Dystrophinopathy should be suspected in a child or adult with the following clinical signs/symptoms:  progressive skeletal muscle weakness, increased CPK, intellectual impairment, myalgias, or cardiomyopathy.

3. BMD patients by convention ambulate after 16.  In 40 + year olds, isolated quad weakness can be confused with IBM.  EKG findings are similar to DMD  (arrythmias or decreased EF requiring Ace inhibitors).  Chronic respiratory insufficiency can be associated with right heart failure.

4.  Minimally symptomatic BMD with exertional intolerance, myalgia, myoglobinuria, or elevated CK diagnostic yield increases with subtle signs such as clumsy as child, toe walking, positive family history, calf or tongue hypertrophy, or myopathic units on EMG. 

5.  All patients regardless of symptoms should have periodic pulmonary function testing, EKG, and echocardiography.

6.  Vaccinations including pneumococcal and influenza are recommended with low threshold for treating potential infections with antibiotics.

7.  Anesthetic risks mandate patients wear a med alert bracelet. These risks are minimized with nondepolarizing muscle relaxants. 

8.  Bowel program plus suction continuous via gj tube reduces abdominal pain.  Restricted jaw opening can mandate placement of a tube. 

9. Consider seated position or other creative safety measures during surgery if possible and if indicated.

10.  PT with range of motion and stretching exercises are hallmark.

Autosomal dominant ataxias with known causation

Most common types are SCA I,II, III, VI which comprise > 50 % cases in USA.  * indicates caused by polyglutamine CAG repeat expansion

SCA I--*-- begins as gait disorder, progresses to four extremity ataxia with dysarthria leaving patient wheelchair bound within 15-20 years.There is phenotypic variability and anticipation (genetically).  Clinically there is involvement of cerebellum with neuronal dropout of Purkinje cell layer and clinical involvement of the brainstem.  No supratentotial involvement.  Not as common as type II but well worked out molecularly,

SCA II--*--characterized by ataxia, dysarthria, slow saccades and neuropathy.  Originally Cuban description.  Very common worldwide, especially in India.  Slow saccades are not pathognomonic, they also are seen in SCA I and III.   Dementia, areflexia, myokymia also are seen. Gene expansion includes cytoplasmic protein ataxin, function of which is unknown.  Anticipation is marked, and disease may present in one generation in old age, in the next much earlier.  Number of repeats are 35-77 , with 32-34 "zone of reduced penetrance."

SCA III--*--Very common, is aka Machado-Joseph disease.  Presents with ataxia, eye movement abnormalities (bulging eyes, opthalmoparesis, staring eyes), speech and swallowing abnormalities.  Pathologic abnormalities include cerebellar afferent and efferents, pontine and dentate nuclei, substantia nigra, subthalamic, GP, cranial motor nuclei and anterior horn cells.  Ataxin 3 gene is at fault.  Repeats: normal 12-42, high is 52-84.  Early onset rigidity and dystonia (largest expansions), middle onset adult ataxia, late onset neuropathy (smallest expansions).  A few patients have Parkinson's that is dopamine responsive and even fewer have RLS.  Peripheral involvement is especially variable.  MRI shows range from fourth ventricle enlargement to severe olive sparing spino pontine cerebellar atrophy.

SCA-- V-- "Lincoln family ataxia"--slowly progressive dominant ataxia found in grandparents of Lincoln.  SPTBN2 gene ecoding B III spectrin is at fault. 

SCA VI  --*--  milder disease, pure cerebellar associated with normal lifespan.  Presentation is gaze evoked nystagmus, dysarthria, onset at age 50 or so, impaired vibratory and position sense.Its fairly common in Japan and in Germany.  Caused by expansion/repeat in voltage dependent calcium channel,same gene  that causes episodic ataxia type 2 and familial hemiplegic migraine.  However, mutations in these conditions in the same gene are different mutations.

SCA 7--*-- cerebellar brainstem disease associated with retinal degeneration and blindness.  It has striking instability of transmission especially with paternal transmission, with cases in utero and in childhood.

SCA 8--*-- classical presentation of disease with gait and limb ataxia, swallowing speech and eye movement abnormalities.  Most have progressive ataxia.

SCA 10 --*-- Mexicans with cerebellar symptoms and seizures.  Extremely large expansion is found in SCA 10 gene. Ashizawa.

SCA 11--*--  2 British families reported with benign gait and limb ataxia.  TTBK2 gene.

SCA 12 --*--PP2R2 gene with dominant ataxia presenting with upper extremity tremor, progressing to head tremor, bradykinesia, abnormal eye movements.  Onset 8-55 years.

SCA 13 --*-- dominant ataxia, may present in childhood with MR, dysarthria, nystagmus, +/- hyperreflexia.  Due to KCNC3 gene mutation in voltage gated K channel subunit.

SCA 14 --not repeat--slowly progressive ataxia with dysarthria in early adulthood.  May be pure cerebellar or accompanied by myokymia, hyperreflexia, axial myoclonus, dystonia and vibratory sense loss. 

SCA 15-16-- allelic (ie same allele) disorder occurring in Austrailian and Japanese families, slowly progressive pure cerebellar disorder.  Dysarthria, horizontal gaze evoked nystagmus, sometimes head tremor.  Disease is due to deletions in IPTR gene

SCA 17 --*--Widespread cerebral/cerebellar dysfunction, rare in US, more common in Japan.  Presents with gait and limb ataxia, psychiatric dysfunction, EPS, seizures, may resemble Huntington;s disease.  MRI shows widespread cerebral and cerebellar dysfunction.  Onset in mid to young adulthood.

SCA 26 -- Norwegian pure cerebellar ataxia that maps closely to gene affecting Cayman ataxia and SCA 6 with Purkinje cell degeneration. 

SCA 27-- Dutch disease manifests with hand tremor in childhood.

DRPLA-- *--  progressive ataxia, choreoathetosis, dementia, seizures, myoclonus, and dystonia. Before age 20 there are almost always seizures and a progressive myoclonic seizure like presentation.  Older patients get ataxia with choreoathetosis and dementia.  More common in Japan, but Haw River phenotype is an African American family in the Carolinas with seizures and cerebral calcifications.

episodic ataxias--EA1 and EA2 are due to mutations in K and Ca channel genes.  EA1-- patients ahve minutes of ataxia due to stress, exercise or change in posture. Patients also may have myokymia.   KCNA1 gene. EA2 has ataxia that lasts days , precipitated by stress, exercise or fatigue and is due to mutation of same gene as SCA 6 (CACNA1A4 gene). Acetozolamide may help.  Other EA's with prominent vertigo also are described.

Friedrich's ataxia, FARR, LOFA, VLOFA

Friedrich's ataxia (AR) is subclassified into classical (75%), FARR (FA with retained reflexes, adult onset), LOFA (late onset FA) and VLOFA (very late onset FA). 
In FA, pathology involves spinocerebellar tracts, lateral corticospinal tracts, posterior columns but NOT cerebellum.  Clinical features include a.  progressive gait ataxia and scoliosis  b.  gait worse in darkness (posterior column involvement)  and worsening during puberty    c.  dysarthria and hand incoordination   d.  areflexia  e. extensor plantars.  Associated features may include  e.  optic nerve atrophy (25%),  f.  SN hearing loss (10%)  g.  optic flutter or square wave jerks but not opthalmoplegia  h.  hypertrophic cardiomyoapthy (90%)  i. pes cavus  j. diabetes mellitus in 15 % 15 years after onset  j.  wheelchair bound after 15 years  k.  Death 30-70.
In FARR, LOFA, VLOFA, sporadic ataxia occurs without cardiomyopathy. Spasticity occurs, areflexia does not.  Again normal cerebellum.  Sporadic ataxia patients may warrant gene testing for frataxin.  Affected patients usually have 2 affected alleles, carriers have one.  Rarely, sequencing of second allele for FXN is needed to find a point mutation (compound heterozygosity).

Neurosarcoidosis pearls diagnosis

1.  Percent with cranial neuropathy-- 50-75 (most common VII, second II, all can be affected)

 

2.  Percent with parenchymal brain lesions-50

 

3.  Other manifestations - cognitive 20, meningeal 10-20, PN 15, seizures 5-10, spinal 5-10, myopathy 1.4-2.3

 

4.  Neuroendocrine presentations may include polydipsia, polyuria, panhypopituitarism, or massive obesity if sarcoid invades satiety center of hypothalamus

 

5.  Neuropathy can be virtually any type

 

6.  Myopathy can be acute, chronic or nodular and is usually subclinical. In contrast to steroid myopathy (the rule-out diagnosis often), sarcoid myopathy may have palpable nodules, contractures, cramps, elevated CPK, and fibrillation potentials and positive sharp waves on EMG.  Both steroid and sarcoid myopathy will have myopathic potentials.

 

7.  Contrast enhanced MRI to look for meningeal involvement is extremely important, but is not specific.

 

8.  Whole body PET imaging is better than Gallium and can be used to look for lymph nodes suitable for biopsy for diagnosis, but is not specific

 

9. CSF is normal in one third,but can show high protein, lymphocytosis, low glucose. OCB's , high IgG index

 

10.  CSF ACE levels are insensitive (24-55 %) but fairly specific (93%) for CNS sarcoid

 

11.  Heerfordt's syndrome consists of facial palsy, parotid enlargement, uveitis and fever and is considered so typical that tissue biopsy is not required

 

Persistent genital arousal syndrome: neurology of and comparison to epileptic orgasms

This post details  a  neurologic basis  to persistent genital arousal syndrome (PGAS).  The condition is characterised by unwanted repeated multiple daily episodes of sexual arousal, that often leads to dozens or hundreds of orgasms daily, relieved with masturbation briefly before recurring.  It can be lifelong, occur during pregnancy, or in the postmenopausal state.  Precipitating factors include pudendal nerve injury,  and antidepressant drugs including trazodone.  A strong association with restless legs syndrome and overactive bladder has been noted. Treatments that were successful in many patients include clonazepam, tramadol, pelvic floor massage focusing on the pudendal nerve, varenicycline,and pudendal nerve blocks.

This condition can be differentiated from orgasmic seizures, which itself needs to be divided into different entities.  Orgasms as an aura of a seizure can occur usually due to right hippocampal, but occassionally left hippocampal or left parietal epilepsy.  Reflex epilepsy after orgasm also occurs again usually after right temporal but occassionally left frontal seizures and in one case report reflected the manifestations of complete heart block, cured with a pacemaker.  Reflex epilepsy occurring as orgasmic aura has been reported after toothbrushing in one Taiwanese patient.

see pub med for references

Antiepileptic drugs and peripheral neuropathy

Effects of the antiepileptic drugs on peripheral nerve function; Boylu E, Domaç FM, Misirli H, Senol MG, Saraçoglu M; Acta Neurologica Scandinavica 121 (1), 7-10 (Jan 2010)

 

Upshot-- carbamazepine, but not valproate, oxcarbazepine and topirimate, affect nerve conduction studies among chronic takers.

Clinical pearls in diagnosis of vestibular disorders

1.  Look for nystagmus with and without fixation.  To achieve latter, either examine in a darkened room with Frenzel glasses or use opthalmoscope in one eye and cover the other.

2.  Nystagmus can be assessed with holding eyes 30 degrees from midline in 4 positions (L-R-U-D) each for 20 seconds.  Further out, and nystagmus is expected.  Use a chart to score.

3.  Nystagmus through eyelids can be confused with lid twitch.

4.  Features of central nystagmus that differ from peripheral include pure vertical, horizontal or rotatory rather than combined;  no effect of fixation;  may change direction;  central abnormality may affect pursuit or OKN. In central nystagmus, there may be a null zone near center after which nystagmus changes direction when eyes look in opposite direction.

5.  Head thust sign is a simple test at bedside, of horizontal component.  Move head rapidly a short distance horizontally in one direction and then other.  Eyes should at start be ten degrees from primary position so that after the thrust they will be near primary position.  Patient fixates on examiner's nose.  If there is a catch up saccade in one direction but not the other, that is evidence of a peripheral lesion on that side. The absence of a head thrust sign suggests a central etiology.

6.  Patients with peripheral lesions veer towards the side of the lesion when up.  Patients with central lesions often cannot stand.  Patients with central lesions are more likely to have dysarthria,  numbness or weakness.

7.  Viral labyrinthitis needs to be diagnosed after ruling out other entities.  Bacterial usually has associated mastoiditis that is identified on CT scans of the temporal bone.  Usually auditory and vestibular function both are affected with bacterial infection.

8.  Recurrent episodes that become bilateral and lead to deafness within months are associated with syphilis.

9.  Perilymh fistula often presents abruptly after a precipitating event, such as head trauma, barotrauma, strain while lifting, or sneezing.  It is very common among patients who have undergone stapedectomy for otosclerosis.  Patients with fluctuating symptoms or positive fistula test need to undergo surgery.

10. Very important: the Dix Hallpike test can be positive in central vertigo cases, including tumors, but features are different.  Central variety fails to attenuate with repeated tests, may last longer than 30 seconds, and may have fast phase downward to cheek (as opposed to peripheral which is to bottom ear and forehead). 

Classical Babinski-like signs

Extensor toe signs
Babinski response- extension of big toe, fanning of small toes with stroking plantar surface
Chaddock response- same response except stimulation is of lateral foot from lateral malleolus
Gordon leg sign-- same with stimulation of squeezing leg muscle
Oppenheim's sign-- same result with downward stroking of tibia and tibialis anterior muscle
Gonda's reflex--upward movement of big toe by moving another toe down and releasing with snap
Shaefer's sign-- Babinski response by squeezing Achilles' reflex


Non extensor toe  long tract signs
Rossolimo's sign-- same response with striking or tapping the ball of the foot
Mendel-Bechterew sign- flexion of 4 outer toes by striking dorsum of foot
Hoffman's sign-- Clawing of the thumb and all fingers by flicking distal phalanx of index finger
Gordon's finger sign-- flexion of fingers or thumb/index finger with pressure over pisiform bone
Chaddock's wrist sign- wrist flexion, extension & fanning of fingers with stimulation of ulnar side of hand
Hirschberg's sign- adduction and internal rotation while stroking the inner border of foot
Ankle clonus-- may be normal if unsustained
Patellar clonus (trepidation sign)-- lifting relaxed knee suddenly looking for increased tone

Other pathologic signs
Beevor's sign-- with lesion at T10, the patient tenses abdominal muscles and ombilicus moves upwa rds, doe to paralyzed
Mass reflex of Riddoch-sudden emptying of bowel and bladder, flexion of lower limbs and sweating.  Its released pathologically by severing spinal cord and striking skin below

Classical abnormal gaits

Tabetic (ataxic) gait
Hemiplegic gait
Steppage gait
Scissors gait
Drunken or ataxic gait
Waddling or clumsy gait
Festinating gait
Hysterical gait
astasia - abasia

metoprolol : no effect on QOL in recurrent syncope

Effect of metoprolol on quality of life in the prevention of syncope trial; Sheldon RS, Amuah JE, Connolly SJ, Rose S, Morillo CA, Talajic M, Kus T, Fouad-Tarazi F, Klingenheben T, Krahn AD, Koshman ML, Ritchie D; Journal of Cardiovascular Electrophysiology 20 (10), 1083-8 (Oct 2009)

INTRODUCTION: Vasovagal syncope is common, often recurrent, and reduces quality of life. No therapies have proven useful to improve quality of life in adequately designed randomized clinical trials. Beta-blockers have mixed evidence for effectiveness in preventing syncope. METHODS: The Prevention of Syncope Trial was a randomized, placebo-controlled, double-blind, multinational, clinical trial that tested the hypothesis that metoprolol improves quality of life in adult patients with vasovagal syncope in a 1-year observation period. Randomization was stratified in strata of patients<42 and>or =42 years old. The quality of life questionnaires Short Form-36 (SF-36) and Euroqol EQ-5D were completed at baseline and after 6 and 12 months of treatment by 204, 132, and 121 patients, respectively. RESULTS: There were 208 patients, mean age 42 +/- 18, of whom 134 (64%) were females. All had positive tilt tests. There was no improvement in quality of life during the trial in the entire group or in either treatment arm. Patients in the metoprolol treatment arm did not have improved quality of life compared to the patients in the placebo arm using either the SF-36 or EQ5D after either 6 or 12 months. Finally, there was no improvement in quality of life associated with metoprolol use in patients either<42 or>or =42 years of age. CONCLUSION: Metoprolol does not improve quality of life in patients with recurrent vasovagal syncope and a positive tilt test.

ED treatment of migraines: i-v prochlorperazine plus Benadryl beats sumatriptan

A Prospective, Randomized Trial of Intravenous Prochlorperazine Versus Subcutaneous Sumatriptan in Acute Migraine Therapy in the Emergency Department; Gutierrez FJ, Rieg TS, Moore TS, Gendron RT, Kostic MA; Annals of Emergency Medicine (Dec 2009)

STUDY OBJECTIVE: Intravenous (IV) prochlorperazine with diphenhydramine is superior to subcutaneous sumatriptan in the treatment of migraine patients presenting to the emergency department (ED). METHODS: In this randomized, double-blind, placebo-controlled trial, after providing written informed consent, patients presenting to the ED with a chief complaint of migraine received a 500-mL bolus of IV saline solution and either 10 mg prochlorperazine with 12.5 mg diphenhydramine IV plus saline solution placebo subcutaneously or saline solution placebo IV plus 6 mg sumatriptan subcutaneously. Pain intensity was assessed with 100-mm visual analog scales (visual analog scale at baseline and every 20 minutes for 80 minutes). The primary outcome was change in pain intensity from baseline to 80 minutes or time of ED discharge if subjects remained in the ED for fewer than 80 minutes after treatment. Sedation and nausea were assessed every 20 minutes with visual analog scale scales, and subjects were contacted within 72 hours to assess headache recurrence. RESULTS: Sixty-eight subjects entered the trial, with complete data for 66 subjects. Baseline pain scores were similar for the prochlorperazine/diphenhydramine and sumatriptan groups (76 versus 71 mm). Mean reductions in pain intensity at 80 minutes or time of ED discharge were 73 mm for the prochlorperazine/diphenhydramine group and 50 mm for those receiving sumatriptan (mean difference 23 mm; 95% confidence interval 11 to 36 mm). Sedation, nausea, and headache recurrence rates were similar. CONCLUSION: IV prochlorperazine with diphenhydramine is superior to subcutaneous sumatriptan in the treatment of migraine.

seroquel for refractory migrained pilot study

An Open Pilot Study Assessing the Benefits of Quetiapine for the Prevention of Migraine Refractory to the Combination of Atenolol, Nortriptyline, and Flunarizine; Krymchantowski AV, Jevoux C, Moreira PF; Pain Medicine (Dec 2009)

Background. Migraine is a prevalent neurological disorder. Although prevention is the core of treatment for most, some patients are refractory to standard therapies. Accordingly, the aim of this study was to evaluate the use of Quetiapine (QTP) in the preventive treatment of refractory migraine, defined as previous unresponsiveness to the combination of atenolol, nortriptyline, and flunarizine. Methods. Thirty-four consecutive patients (30 women and 4 men) with migraine (ICHD-II), fewer than 15 days of headache per month, and not overusing symptomatic medications were studied. All participants had failed to the combination of atenolol (60 mg/day), nortriptyline (25 mg/day), and flunarizine (3 mg/day). Failure was defined as<50% reduction in attack frequency after 10 weeks of treatment. After other medications were discontinued, QTP was initiated at a single daily dose of 25 mg, and then titrated to 75 mg. After 10 weeks, headache frequency, consumption of rescue medications, and adverse events were analyzed. Results. Twenty-nine patients completed the study. Three patients withdrew and two were lost to follow-up. Among those who completed, 22 (75.9%; 64.7% of the intention-to-treat population) had greater than 50% headache reduction. The mean frequency of migraine days decreased from 10.2 to 6.2 per month. Use of rescue medications decreased from 2.3 to 1.2 days/week. Adverse events were reported by nine (31%) patients. Conclusions. Although limited by the open design, this study provides pilot data to support the use of QTP in the preventive treatment of refractory migraine. Controlled studies are necessary to confirm these observations.

Kearn's Sayre syndrome

Rowland's diagnostic criteria

 

Obligate triad

1) Onset before 20

2) Progressive external opthalmoplegia

3) Pigmentary retinopathy

 

plus at least one of:  CSF protein>100, ataxia, cardiac conduction block

 

 

websites for genetic information

http://www.geneclinics.org/

http://www.neuromuscular.wustl.edu/

http://www.pdgene.org/

Neurotoxicology: sources of lead in adults

Lead poisoning occurs due to inhaling inorganic lead salts and fumes in processes involving remelting of lead. These include painting, printing, pottery glazing, lead smelting, welding and storage battery manufacturing. Other cases have occurred in miners, foundry and garage workers especially those who soldered radiators. Aruvedic herbal remedy for arthritis is described. Moonshine whiskey was very common in one series. The presentation is colic, anemia and peripheral neuropathy. It responds somewhat to calcium salts but not morphine (colic). Organic lead poisoning occurs in those who clean gasoline storage containers with insomnia, hallucinations, delusions and irritability. Hematologic changes are not found, and its usually reversible.

Stiff man syndrome (stiff person syndrome) Pearls

1. Insidious onset, then robotic appearance to walking and exaggerated lumbar lordosis in middle aged. Attempted passive movement causes a unique rock like immobility.

2. Trismus does not occur, and eye movements are not affected. Noise may precipitate an attack. Reflexes are normal, and lumbar spine is stiff on exam.

3. "Stiff limb" in one leg, spreading to other, has same antibodies (anti GAD) is similar to lcoalized tetanus.

4. EMG is normal and spasms disappear during sleep and anesthesia, differentiating from myokymia and Isaac's syndrome.

5. Rare paraneoplastic form usually accompanies breast cancer with antibodies to amphiphysin or gephyrin (proteins related to synaptic GABA receptors) and may be accompanied by opsoclonus or encephalopathy.

6. Differential diagnosis includes tetanus, Isaac's syndrome and myoclonic spinal neuronitis.

7. An infantile form starts at age 2 months and disappears by age 2.

Lysosomal storage diseases in adults

1. Of 45 or so diseases, all are autosomal recessive except the 3 that are X linked, namely Hunter's disease (mucopolysaccharadosis type II), Fabry's, and X linked myopathy with cardiomyopathy (lysosomal associated membrane protein 2, or LAMP 2).

2. GM2 can resemble Friedrich's ataxia, but unlike Friedrich's has hyperreflexia, episodic psychosis, and absent cardiomyopathy and scoliosis which should give away the diagnosis.

3. Dementia is common, and is a presenting feature of Kuf's disease type M and adult onset MLD. Dementia is most common presenting feature of adult onset mannosidosis, fucosidosis, aspartylglucosaminuria, Niemann Pick type c (along with vertical gaze palsy, dystonia, and dysarthria)

4. Progressive myoclonic epilepsy occurs in Kufs disease type A with spike wave on EEG and photosensitivity at low flash frequencies (see Berkovic 1988 Brain for review article).  Type B is characterized by dementia, ataxia,  EPS and facial dyskinesias.  Sialodosis type I aka cherry red spot myoclonus has treatment resistant epilepsy with macular cherry red spot and abnormal neuraminidase in skin fibroblasts.

5.  Late onset myopathy occurs in Pompe's disease, with high CPK, accumulated glycogen in vesicles, and deficient alpha glucosidase which is hard to measure.  Danon disease is X linked recessive and has hypertrophic cardiomyopathy and muscle weakness, and muscle biopsy shows autophagic vacuoles with glycogen. Its due to LAMP 2 deficiency.  There is mild MR and usually, death before 30. 

Managing adults with hydrocephalus : pearls

This post assumes patients who received a shunt as a child has problems as an adult

1. Signs of shunt malfunction/ increased ICP. On PE look for VI n palsy, papilledema, +/- reliability of shunt pump test

2. On history consider HA worse in AM or with recumbency, associated vomiting with relief, and diplopia suggest raised intracranial pressure. If HA is worse when up, consider low pressure headache

3. On imaging, assess all 4 ventricles independently, look for periventricular edema, edema around proximal shunt tip, loss of cerebral sulcal pattern near vertex, or loss of CSF spaces in basal cistern and Sylvian fissure. ALWAYS compare to prior scan closely.

4. ETV or endoscopic third ventriculostomy is used in some patients especially with third ventricular obstructions. ETV has a risk of catastrophe, a higher risk of immediate failure, a lower risk of long term failure but still can obstruct years later (unlike most standard shunts). ETV has the compelling advantage of a lower infection risk.

5. Patients with myelomeningocoele should be evaluated in a top down manner: shunt obstruction, Chiari malformation, syringomyelia/syringobulbia, and tethered cord. Often neurosurgeons will want to surgically manage the shunt to make sure it is working before embarking on other issues in these cases. An example case in Continuum was a patient who had presented with hand weakness and syringomyelia, but who had massively dilated ventricles and whose primary problem was in fact the shunt dysfunction.

Fragile X tremor ataxia syndrome (FXTAS)

FXTAS is due to premutation, and an excess amount of FRMP protein (50-200 repeats). Not all carriers develop FXTAS. Features include

1. usually presents with intention or action tremor with handwriting or using utensils

2. above is followed by ataxia with falls and unstable gait
above occurs in male carriers at a rate of 17% by 50's, 38 % by 60's, 47 % by 70's and 75 % by 80's. Women have less FXTAS with 8 % of those with premutation affected.

Other neurologic features
1. painful neuropathy

2. autonomic dusfunction (erectile dysfunction, hypertension, OH, urinary urgency and frequency, and incontinence.  Girls develop premature ovarian insufficiency or POI. 

3. White matter abnormalities (increased T2 intensity)especially bilateral cerebellar peduncles but elsewhere in deep white matter(seen in 60 % males, 13 % of females)

4. Executive dysfunction, short term memory loss, disinhibition and dementia

5. Unique eosinophilic intranuclear inclusions in neurons and astrocytes especially in the hippocampus and in the limbic system that are tau negative. They also occur in the PNS including the pericardiac and mesenteric ganglia and Leydig cells of testes.

6. Testosterone deficiency

7. Anxiety, social phobia and depression

8. Women with FXTAS : 43 % have fibromyalgia and 50 % have thyroid disease usually hypothyroidism

9. 2-3 per 100 develop multiple sclerosis and some develop Alzheimers

Treatment: SSRI's for anxiety, lithium for depression

Fragile X syndrome (FXS) clinical features

1. long face
2. prominent long ear pinnae
3. high arched palate
4. mitral valve prolapse
5. dilated aortic arch
6. flat feet
7. hyperextensible finger joints in childhood
8. macroorchidism (testicular volume greater than 30 cc in adulthood)
9. soft or velvet like skin.
10. Daughters can receive premutation only, sons cannot receive gene from their father
11. Single palmar crease

rare problems-- elasticity leads to increased hernias, and dilation of ureteric root leads to hydronephrosis.

Neuropsych
1. hyperarousal to stimuli with increased sympathetic response
2. Agression, anxiety
3. Concrete thinking
4. Dramatic decline of cognition in middle or later life, due to FRMP regulating amyloid precursor protein (APP) leading to coexisting Alzheimer's disease
5. Men typically are not sexually active and do not marry (not invariable)