risk factors for statin myopathy; antibodies of

The field of autoantibodies related to immune-mediated inflammatory myopathies has expanded in recent years and there is now a host of antibodies that have relevance to these myopathies. The 1975 Bohan and Peter criteria for the classification of immune-mediated inflammatory myopathies do not reflect many newer insights, and several newer classification schemes exist, but none enjoy uniform acceptance.¹² Some controversy remains as to the pathophysiology behind dermatomyositis, but this disease is probably the most consistently defined. Conversely, polymyositis has several varied definitions, and in the Bohan and Peter criteria it was not delineated from inclusion body myopathy (IBM). The antisynthetase syndrome associated with antibodies described in this section does not cleanly sort under either the dermato- or polymyositis labels. The inflammatory myopathies associated with SRP and 200/100 antibodies do not even necessarily have the inflammatory muscle infiltrates that we traditionally associate with inflammatory myopathies. While IBM has prominent inflammatory features, none of the described autoantibodies are linked to IBM, nor is immunomodulatory treatment of any benefit. For these and other reasons, many authorities believe IBM to be more of a myodegenerative disease with secondary inflammation.¹³ Granulomatous myopathy, HIV-associated myositis, and graft vs host disease are other immune-mediated inflammatory myopathies without associated muscle-directed antibodies.

There are also the overlap syndromes in which another defined autoimmune condition exists and overlaps with a myositis. This can occur in diseases such as systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and Sjögren syndrome. Distinguishing the primary inflammatory myopathies from the overlap syndromes is done by excluding the conditions causing overlap syndromes, but there are also autoantibodies that are almost unique to the immune-mediated inflammatory myopathies referred to as muscle-specific autoantibodies (MSA). Other antibodies are frequently seen in other connective tissue disorders, and these can be referred to as myositis-associated autoantibodies (MAA). All of these antibodies can help establish the diagnosis of myositis when the muscle biopsy is inconclusive, and the MSAs as well as some of the MAAs are listed in table 2.

The most prevalent MSA is the anti-Jo antibody, which is directed against histidyl-tRNA synthetase. Anti-Jo is detected in about 20% of patients with myositis in most populations. Anti-Jo can be detected in both dermatomyositis and polymyositis and is frequently associated with interstitial lung disease and mechanic's hands. This clinical and laboratory constellation is referred to as the antisynthetase syndrome. Interstitial lung disease is a potentially fatal comorbidity that often requires more aggressive immunomodulatory treatment. Histologically, the inflammation is often more perimysial rather than endomysial.¹⁴ There are other newer antisynthetase antibodies with similar clinical features including those that recognize threonyl-tRNA synthetase (anti-PL-7), alanyl-tRNA synthetase (anti-PL-12), glycyl-tRNA synthetase (anti-EJ), isoleucyl-tRNA synthetase (anti-OJ), asparaginyl-tRNA synthetase (anti-KS), anti-tyrosyl-tRNA synthetase, and antiphenylalanyl synthetase (anti-Zo). These other antibodies are each present in a few percent of patients, but there is essentially no overlap between them and patients do not express more than one antisynthetase antibody. A different type of antibody is the Anti-Mi-2 autoantibody. This nuclear antibody is directed against a component of the nucleosome-remodeling deacetylase, is seen more often in dermatomyositis, and is infrequent in most populations.

A clinically useful antibody is the SRP antibody. This antibody can often be found when there is myonecrosis, but little or no inflammation is seen on muscle histology. Identifying the antibody can be helpful in establishing that the myopathy is inflammatory and encourages escalating immunosuppression even if initial attempts are unsuccessful. The target of the new anti-155/140 antibody remains unknown, but this antibody is seen in dermatomyositis and is more common in paraneoplastic dermatomyositis compared to idiopathic autoimmune dermatomyositis.¹⁵ The not yet commercially available anti-200/100 autoantibody appears to have specificity for the necrotizing statin myositis (discussed earlier).⁸ In patients with a myopathy of unclear cause and a nondiagnostic biopsy testing, one should consider testing the anti-Jo antibody and a comprehensive panel of the other MSA, either sequentially or simultaneously

Myopathy: Five New Things

• Risk of statin toxicity increases along with increases in their lipophilicity, cholesterol-lowering potency, and dosage.
• In immune-mediated statin myopathy, discontinuation does not translate into immediate recovery.
• MRI and muscle ultrasound in myopathy may provide detailed anatomic information.
• Autoantibody testing may be helpful in defining myopathies of unclear cause.
• Enzyme replacement may improve function in Pompe disease.

vincristine neuropathy nuggets and pearls

Verstappen CCP,Heimans Koeppen S, et al. JJ,  Dose-related vincristine-induced peripheral neuropathy with unexpected off-therapy worseningNeurology March 22, 2005 vol. 64 no. 6 1076-1077

 

Article described microtubule related neuropathy due to vincristine in 114 patients. 

 

1.  High dose group experienced more signs and symptoms than low dose group.

2.  Off therapy worsening signs and symptoms occurred in about 30 percent, mostly in the first month off. Most patients improved off therapy however.

3.  Paresthesias and numbness in both groups developed earlier in hands than feel and were more prominent in hands

4.  Paresthesias, numbness and pain occurred at more than 50 percent in both groups

5.  Resulting physical limitations include trouble buttoning clothes, climbing stairs, writing and walking

6. The dose intensity of VCR has changed considerably over the years. Studies 30 years ago describe dose intensities of 2 to 4 mg/week, frequently leading to a severe mixed sensorimotor peripheral neuropathy.Today, VCR is usually administered in a dose of ≤2 mg once every 1 to 4 weeks.

7.  Off therapy deterioration is also well described in cisplatin and paclitaxol related neuropathy.

 

 

 

 

Sjogren's Pearls

J. Birnbaum. Peripheral nervous system manifestations of Sjogren syndrome: clinical patterns, diagnostic paradigms, etiopathogenesis, and therapeutic strategies. The Neurologist 2010; 16:5:287 -- 297 .

1.Syndromes that can cause sicca symptoms and which should be typically excluded, include hepatitis B or hepatitis C, HIV, sarcoidosis, and a history of radiation to either the header the neck.

2. 30% to 50% of patients have negative auto antibodies and require a lip biopsy for diagnosis.

3.  Sensory ganglionapathy : aka sensory  neuronopathy is dramatic with isolated or disproportionate impairment of kinesthetic awareness, with profound handicap of proprioception, even affecting the larger joints. Sensory deafferentation can cause patients to become wheelchair-bound, or have pseudoathetoid movements which may be misdiagnosed as a movement disorder. The most common presentation is distal dysesthesias.  Differential diagnosis includes paraneoplastic syndromes, Bickerstaff brainstem encephalitis, and effect of drugs for example, cisplatin and pyridoxine. Nerve conduction studies typically absent sensory nerve action potential(snaps) and preserved compound motor action potentials (cmap). T2 hyper intensities in the dorsal spinal cord are described. Response to I VIG is inconsistent.

4.  Small fiber neuropathy: the cardinal feature can be excruciating burning pain. There is disproportionate or selective impairment in pinprick and temperature with preserved vibratory sense and proprioception. The onset is subacute or chronic usually. The differential diagnosis includes diabetes, amyloidosis, chemotherapy and other medications, genetic syndromes (i.e. Fabry's) and complications from HIV treatment.

5.  Patients with findings of small fiber dysfunction disproportionally affecting the proximal extremities, torso or face in unorthodox patterns may have Sjogren's. Patients may also have classic length dependent symptoms.

6.   Sjogrens and vasculitis: patients with mononeuritis multiplex should be evaluated for cryoglobulinemia especially with high titer rheumatoid factor, with disproportionate C-4 hypo-complementemia, or normal C-3. Small vessel vasculitis and low levels of C-4 complement in Sjogren's space placed the patient at 6 to 40.  fold risk for non-Hodgkin's lymphoma. Therefore the development of systemic features such as fever or weight loss merit close scrutiny. Nerve or muscle biopsy showing vasculitis more likely responds to immunosuppressive therapy. Mori described patients with axonal MMN who also had cranial neuropathies. The most common is trigeminal neuropathy  which may be indolent, progressive, or bilateral. The unifying feature may be ganglionapathy.  Facial nerve also may be affected. Acute cranial neuropathy plus rapid multiple mono neuropathies may prompt concern for vasculitis.

7. Demyelinating neuropathies are rare but may be noted subclinically. EMG may know isolated prolonged F. waves.
8. Autonomic features are seen in 50% of Sjogren's patients. Inquire about urinary frequency or hesitancy, erectile dysfunction, increased or decreased sweating, orthostatic or temperature intolerance, constipation or increased bowel movements. Adie's pupil , space orthostatic hypotension, and abnormal sweating occurs in 57, 40, and 70% of patients with sensory neuronopathy respectively.

9. Anti-nicotinic ganglionic receptor antibody role is under investigation in Sjogren's. This antibody differs from the anti-muscarinic receptor antibody seen in myasthenia gravis.

10. Inflammatory myopathies occur only in 1 to 2%. Myalgias  may be caused by autoimmune thyroid disease, vitamin D. deficiency, or fibromyalgia. Always assess vitamin D level. Vitamin D may be low due to malabsorption, bacterial deconjugation of bile acids due to gastric motility seen in autonomic neuropathies, type one renal tubular acidosis or coexisting celiac sprue.

Clinical utility of seropositive voltage gated calcium chanell complex antibody

Jammoul A, Shayya L, Mente K et al.  Neurology Clinical Practice  2016; 6:409-418.

Authors differentiate "classic" group with limbic encephalitis or neuromyotonia (9.6% of total) and note the others had a panoply of diagnoses that were nonclassic.  The classic group was more likely to have high titers of ab, but there was overlap.  91 % of lcassic and 21 % of nonclassic had levels > 0.25 nM.  75 % of patietns in high level ab group had autoimmune disorders, and 75 % of patients with low level titers did not.  26 % of patients had a remote malignancy (active, remote, solid or hematologic) but not ab titer difference was noted among the groups . 

Conclusions:  1.  High VGKC ab levels are found in patients with classic and other autoimmune disorderes,  Low level ab titers are seen in nonspecific and mostly nonautoimmune disorders

2.  The presence of VGKC antibodies rather than the level may serve as a marker of malignancy

Notes this is bad on a chart review of 6,032 patients who underwent evaluation . 

The nonclassic group includes PNS and CNS diorders including neuropathy, dementia, ALS, CJD.  Some patietns had nonspecific symptoms such as stutering speech, nausea and vomting and orthostasis without diagnosis of neurologic disease. 

Cancers were oftendiagnosed due towhole body CT/PET; 2 patietns had previously unknown cancer (Ovarian and lung).  Cancer occurred more commonly in those over age 45.  Many cases of ab finding were remote by over ten years from actual tumor.

Clinical spectrum of voltage gated potassium channel (VGKC) autoimmunity

Tan KM, Lennon et al. Neurology 2008; 70:1883-1890. 

80 patients were found, 71 with clinical information available.  Mean age 65.

Neurologic symptoms were subacute or chronic including

1.  cognitive impairment 71 %-- see below

2.  seizures 58 %-- several types

3.  dysautonomia 33 %

4.  myoclonus  29 %

5.  dyssomnia 26 %

6.  peripheral nerve dysfunction 25 %

7.  EPS 21 %

8.  brainstem/cranial nerve dysfunction 19 %-- vision loss/blurred vision, diplopia, dysarthria, hemifacial spasm, facial numbness, anosmia.

9.  hypothalamic involvement-- 38 %-- hyponatremia (36 %) , hyperphagia, (8%) 

Common misdiagnosis was CJD (14 %)..  Other misdiagnoses:  viral encephalitis, recurrent TGA, generalized anxiety disorder, conversion disorder.

Associated tumors (paraneoplastic) 33 % confirmed histologically

carcinoma 18, adenoma 5, thymoma1, hematologic 3.

Associations

hyponatremia  36 %

other organ specific autoantibodies 49 %

coexisting autoimmune disorder 33 % (thyroiditis, DM)

34/38 responded to immunotherapy, half "vigorously" so.

Classic reports of association:

1.  Morvan's syndrome

2,  acquired neuromyotonia

3.  epilepsy

4.  limbic encephalitis

5.  dysatuonomia

6.  lung carcinoma
7. FACIAL BRACHIAL DYSTONIC SEIZURE

Cognitive presentation:

1.  frontosubcortical (personaltiy change, disinhibition,  executive dysfunction) 13 %

2.  Visual hallucination (10 %)

3.  Depression or agitation (13 %)

Treatment of orthostatic hypotension in Parkinson's disease

Source: Neurology 2009 supplement cited above, p.S83

 

1. Consider a role for medication, including selegeline, levodopa, DA agonists and MAO inhibitors.

2.  Increase sodium intake, especially in daytime.

3.  Avoid lying flat which leads to release of renin. Elevate HOB and legs.

4.  Postprandial hypotension can be avoided with small meals, with low carbohydrate intake and avoiding alcohol

5.  Caffeine with breakfast can be helpful

6.  Heat related vasodilatation, vasovagal activities (straining at stool, playing wind instruments, singing all can be considered/limited if applicable.

7.  Isometric exercise especially swimming

8.  Avoid knee high TEDS, consider waist high Jobst stockings or abdominal binders.

 

Medication:

1. Florinef up to 0.5 (start with 0.1 mg).

2. DDAVP 5-40 ug intranasally at bedtime can be tried.  Monitor Na+ in first 4-5 days of treatment and monthly thereafter.  It can cause a severe and life threatening hyponatremia.

3.  Midodrine, start at 2.5 mg per day, do not go above 10 tid, and do not give at bedtime.

4. Erythropoietin 4,000 units biw especially if anemic also.

5.  End of dose sweating can be an "off" phenomenon and can eb treated with more dopamine.

Treating constipation in Parkinson's disease, and urinary problems

Regimen suggested in Neurology 72:21:2009 S4 pp S80-81.

Bowel:

Management consists of dietary changes, exercises and pharmacotherapy.

1.  Dietary changes-- Increase bulk, and soften stool.  Drink 6-8 glasses of water per day.  Increase fiber, decrease baked goods.  @ meals should have high fiber raw vegetables.  Oat bran can be used.  Exercise, including walking, is encouraged. 

 

If stools remain hard, docusate, or lactulose 10-20 grams per day can be used.  Miraelx (otc) can be used.  Patients should be educated about possibble delayed onset and reminded to do the things in paragraph one above. 

 

Third line is milk of magnesia and other laxatives or enemas.  Apomorphine rescue therapy can be used. 

 

Urinary:

Nocturia is earliest problem, then urgency, frequency and hesitancy.  Consider detrusor hyperreflexia v. incomplete/delayed relaxation of the pelvic floor.  Supine hypertension can also cause pressure natriuresis.  Incomplete emptying can be an "off" symptom. UTI should be considered if any change occurs in symptoms. 

 

Avoid nighttime water drinking.  Try Detrol or Ditropan.  Midodrine can worsen symptoms due to increasing sphincter tone.  Diazepan, baclofen or dantrolene can be used to relax sphincter tone occassionally. 

 

neurodoc

Diagnosis of parkinsonism

Classic criteria indicate the triad of resting tremor, akinesia/bradykinesia, and cogwheel rigidity, with two of three being associated with the diagnosis of Parkinson's disease.  At the London Brain bank, the diagnosis was not confirmed in 24 of 100 patients with these premorbid clinical symptoms (Hughes et al., JNNP 1992).  The alternative triad of parkinsonism, assymetry, and response to levodopa correctly identified 98 % in 73 patients reported in a subsequent trial (Hughes et al., Brain 2002) and was therefore considered better. 

 

neurodoc

Optic atrophy helpful hints

 

from AAN 2010 course

differentiate pallor from atrophy

 

segmental patterns

signs of prior disc-- swelling high water marks and gliosis, fuzzy edges,

collateral venous vessels-- retinal choroid collaterals, AION or post pappilledeme

macular exudates pretty "fireworks" around macula

attenuated arterioles-- "ghost vessels" with  gliosis

 

neurodoc

mimics of optic atrophy

from aan course 2010

 

physiologic temporal pallor

aphakia/pseudoaphakia-- after take out lenses after cataract surgery

anemia

myopic discs

optic nerve hypoplasia

myelinated optic nerve fiber layers

 

neurodoc

neuropthy downloads UTAH

http://library.med.utah.edu/NOVEL/

 

neurodoc

MGUS Pearls

from Ramchandren S, Lewis RA.  Monoclonal gammopathy and neuropathy.  Curr Opin Neurol 2009; 22:480-485.

Note-  search this blog for "MGUS" and various information posted elsewhere will not be repeated

Pearl -  Differentiate into subtypes based on type of proteins found, and clinical syndromes

eg.  osteosclerotic myeloma has an 85-100 % incidence of neuropathy, depending on whether they have partial syndrome or full POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M spike and skin changes).  In myeloma one third of patients have subclinical PN, and half of these may be small fiber neuropathy, in others, NCS and EMG is required to detect.  In contrast, PN is much less frequent in Waldenstrom's macroglobulinemia (5-10 %) and amyloidosis (17 %). 

IgM paraprotein patients have half of patients with paraprotein and neuropathy, and 15 % of those with paraprotein and no neuropathy. IgG patients only have 35 % of patients with paraprotein and neuropathy, but 75 % of patients with paraprotein and no neuropathy.  IgA patients have 15 % of those with paraprotein and neuropathy, 10 % of those with paraprotein and no neuropathy.   Thus IgM is NOT the most common paraprotein, but is the most common to cause neuropathy.  Most have MGUS, a few haveWaldenstrom's and  other lymphoproliferative disorders.  IgM binds myelin sheath and neural antigens in patients with IgM and neuropathy, not in those with IgM and no neuropathy.  Of those with IgM paraprotein and neuropathy, half have anti MAG antibodies.  Electron microscopy shows deposition on myelin and separation of myelin by MAG via complement.  Reducing anti MAG IgM also improves the neuropathy. 

IgG paraprotein patients are as above, less likely to develop PN by far, and those that do have all types of neuropathies (distal , length dependent axonal and CIDP).  CIDP patients with IgG paraprotein are otherwise identical to those CIDP patients without IgG paraprotein.  Unless in a patient with myeloma, amyloid or POEMS, IgG paraprotein is likely to be incidental.  A few patients with IgG or IgA paraprotein also have deposition on myelin like IgM patients so previous statement is not absolute.

IgM paraprotein patients with PN usually have kappa light chains and half have anti MAG antibodies.  They are older males (60s) with "DADS" which stands for "distal acquired demyelinating sensory neuropathy."  Large fibers affecting VS and proprioception cause problems with balance that are progressive.  DADS M (DADS with an IgM paraprotein) is probably distinct from DADS no M.  A few patients have an aggressive course.  EMG in DADS M has accentuated distal slowing and long latency motor nerves and attenuated or absent sensory nerves. 

IgG/IgA MGUS have no homogenous presentation, but usually have less balance problems. 

2. Myeloma patients have peripheral neuropathy due to perineural or perivascular IgG kappa deposition, or treatment related neuropathy.  IgM paraprotein is seen rarely in myeloma, and have sensory > motor symptoms.  If amyloid is present, its more likely to be painful.  EP is more likely to show axonal damage, but may show demyelinating sometimes.No intervention changes PN but therapy of MM exacerbates PN. 

3.  POEMS-- Paraprotein is usually IgA or IgG lambda.  Synonyms for condition are Crow-Fukase syndrome or Takatsuki syndrome.  Patients are younger (40s) with severe sensory and motor features.  Presentation is progressive distal weakness, paresthesias, and numbness more often than CIDP like.  Weakness if usually in ankles most severely.  Patients are wheelchair bound within a year.  There is 40 % mortality at five years.  EMG shows demyelination with secondary axonal loss. Conduction block is rare. Nerve biopsy can show endoneurial deposits.  Treatment is for underlying, and PN is reversible for localized process such as plasmacytoma.  High dose chemotherapy with autologous blood stem cell rescue is being explored.  Misdiagnosed early as CIDP.  Diagnosis of: demyelinating PN, monoclonal gammopathy and one of the three:  osteosclerotic myeloma, Castleman's disease or increased VEGF.  Also must have one or more of following:  organomegaly, endocrine dysfunction, edema , skin changes (hypertrichosis or hyperpigmentation), papilledema, thrombocytosis, polycythemia). 

4.  Waldenstrom's is rarely associated with PN but when it is, its usually IgM kappa with or withour anti MAG antibodies.  Its clinically indistinguishable from MGUS related PN with anti MAG or DADS M.  Responds to plasma exchange since IgM paraprotein is intravascular, may also use steroids and alkylating agents and Rituxan.

5.  Amyloidosis PN is usually present for a long time first.  A. is a multisystem disorder with IgG or IgA lambda paraproteins and deposition of light chains in target organs.  Either vascular insufficiency or toxicity of amyloid causes the PN.  Painful progressive distal sensory and motor PN  often with autonomic findings is seen.  NCS show axonal sensory > motor neuropathy.  Mean prognosis is 25 months. 

6.  Patients with DADS and IgG or IgA MGUS respond to treatment regimens used for CIDP patients without MGUS.  DADS M polyneuropathy may be misdiagnosed as CIDP but respond more poorly to treatment regimens used for CIDP.

7.  CANOMAD is a rare disorder (chronic ataxic neuropathy with opthalmoplegia, M protein, cold agglutinins, and anti disialosyl antibodies against gangliosides, including GD1b, GD3, GQ1b, and GT1b.  There is a chronic PN with sensory ataxia and areflexia, with sparing of strength.  Its similar to Miller Fisher syndrome that has antibodies to GQ1b, but is chronic and progressive rather than monophasic and acute. 

Normal pressure hydrocephalus assessments

Questionnaire/assessment: (from the Neurologist)
http://neuropsychminutiae.blogspot.com/2010/07/nph-questionnaires-for-initial.html

Guidelines for the Initial Management of NPH (published in Neurosurgery)  2005; 57:3.

Links, support groups, information, etc.
http://www.ninds.nih.gov/disorders/normal_pressure_hydrocephalus/normal_pressure_hydrocephalus.htm


Well done powerpoint presentation
http://www.usafp.org/USAFP-Lectures/2007-Lectures/16%20March%20-%20Friday/Ryan%20-%20NPHredo.ppt

MRI criteria:

1. Maximal frontal horn width divided by diameter of inner table, usually >.33, but often > .4
2. Lack cortical/hippocampal atrophy/extensive white matter lesions
3. Callosal angle > 40 degrees
4. Altered brain water content
5. Aqueductal and fourth ventricular flow void on MRI

Gait criteria:  At least two of the following

1. Gait/Balance- at least two of following present
2. Decreased step height
3. Decreased step length
4. Decreased cadence/speed
5. Decreased trunk sway
6. Widened stance
7. Toes turned outward while walking
8. En bloc turning- turns take three or more steps
9. Impaired balance- two or more corrective steps for eight steps on tandem gait testing

Cognition (at least two of following)

1. Cognition- two of following present
2. Psychomotor slowing
3. Decreased fine motor speed
4. Decreased fine motor accuracy
5. Difficulty dividing or maintaining attention
6. Impaired recall especially for recent events
7. Impairment of executive functions- multi-step procedures, working memory, formulation of abstractions, insight
8. Behavioral or personality changes

Urinary symptoms: one of following

 

1. Episodic urinary incontinence not attributable to other causes
2. Persistent urinary incontinence
3. Fecal and urinary incontinence

OR  One of following

1. Urinary urgency
2. Urinary frequency- 6 or more voids in 12 hour period
3. Nocturia- more than two voids in night

 Clinical diagnosis

Probable iNPH:  Gait or balance impairment, plus cognitive or bladder control disturbance, or both.  MRI shows an Evans ratio of greater than .3 with no evidence of obstruction.  Diagnosis based on probable NPH predictes 48-64 % of time a good response to surgery.

 

Possible iNPHL  Urinary or cognitive impairment without gait impairment

 

Pearls:

1. Rely on family assessment as much as what patient says about gait assessment
2. Levodopa trial occassionally needed to sort out festination
3. TInetti Assessment Scale (TAT) for gait assessment screening has a B level of evidence from AAN reviews  and is found here:  http://agrc.ucsf.edu/files/Tinetti%20AssessmentTool%20(gait%20and%20balance%20test)%20(Week%202%20-Mobility).pdf
4. TAT misses a velocity component for gait assessment so also use TUG (timed get up and go) and is found here http://www.dhmc.org/dhmc-internet-upload/file_collection/tug_0109.pdf that also has a Level B evidence from AAN
5. Other instruments that can be used are the ten minute walk, Berg balance test  http://www.fallpreventiontaskforce.org/pdf/BergBalanceScale.pdf  and the Short Physical Performance Battery   http://www.grc.nia.nih.gov/branches/ledb/sppb/index.htm
6. Urinary incontinence may be described as urinating just before reaching the toilet
7. Cognitive differentiation from Alzheimer's disease can be accomplished by testing that includes factors that innclude components that should not be affected by NPH, such as Boston Naming Test (in addition to findings that would be affected such as letter fluency and memory and executive function)
8. Atypical presentations in young may include headache, and poor job performance rather than memory loss.
9. Obstruction of aqueduct or fourth ventricle due to "late onset aqueductal stenosis" may improve with endoscopic third ventriculostomy (ETV).  These patients should NOT undergo LP due to risk of herniation
10. Thinned /  distended callosum may predict shunt responsiveness, may be seen as "bowing" on sagittal views
11. Presence of "B" waves and increased pulse amplitudes correlate with symptomatic iNPH and responsiveness to shunting.  Authors use 48 hours of monitoring followed by 72 hours of drainage.
12. Behaviorally and by fMRI, increased Stroop testing and finger tapping correlates with SMA functional activity
13. Response to serial LP's correlates with 88 % response to surgery.  Can measure with Tinetti and TUG tests (links above) .  With high volume tap, expect improvement in velocity, turning, stride length, number of steps to turn, and tendency to fall, among others.  Test immediately before and after shunt, and again q 2-4 hours.  Consecutive day LP's x 3 days increased sensitivity to 88 %. 
14. ELD (extended lumbar drainage x 3 days) if no response, very few patients will benefit from surgery.
15. With ELF and physiologic measurements, authors claim 75-90 % improvement in first year after shunting, and 80 % sustained improvement after two years, with substantial overall Medicare expenditure savings. 
16. If a programmable shunt is used, the billing code is 62252
17. Obviously need a good neurologist to make the diagnosis and exclude various neurodegenerative diseases

Coin rotation test validation

 

Hill BD et al. The Neurologist. 2010; 16: 249-253

 

Authors validate a longstanding easy test for fine motor processing used for decades at LSU in 86 normals.  Task consists of counting number of 180 degree rotations of a quarter in ten seconds by the dominant and nondominant hands.  A correction for drops is used, but not that important.  Task is to rotate a quarter using thumb and fingers one and two in ten seconds with an examiner using a timer and counting.  If the coin is dropped, the subject gets another ten seconds.  The adjusted score is the number of rotations in ten seconds minus (0.1 x rotations x drops).  Traditionally, LSU has used a cut score of ten to indicate impairment.  Authors believe a cut score (for both hands) of 13 is better, with increased sensitivity and some loss of specificity.

 

Risk of falling in Parkinson's disease patients

from Kerr et al. Neurology 2010; 75: 116=124

Authors looked at 101 independently living patients without walking aids and put various factors through a computer to predict risk of falling.  The factors that increased the risk include

• dyskinesias
• symptomatic orthostasis
• sleep disturbance
• Tinetti, Berg, and TUG (timed up and go) measurements
• poor peripheral sensation and knee extension strength and greater a-p sway when standing on firm surface
• UPDRS total score and FOG (freezing) questionnaire
• For previous nonfallers, key measurement was A-P sway on firm surface as risk for future conversion to falling
• UPDRS factors that were most important were rising from chair, rapid alternating movements and leg agility

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.