Thursday, December 01, 2011

Central pontine myelinolysis PEARLS and SURPRISING FINDINGS

Graff-Radford J, Fugate JE, Kaufmann TJ et al.  Clinical and radiologic correlations of central pontine myelinolysis.  Mayo Clin Proc 2011; 86: 1063-1067.

Authors did a chart review of patients with definite CPM seen at Mayo over 11 years and found 24 cases.  Key points:

1. MRI T2 signal abnormality even if extensive does not predict clinical outcome as some patients with bad MRI recovered. 

2,  Half had CPM only, half also had extrapontine myelinolysis especially thalamic

3.  Causes were rapid correction of Na  (67%), hyperosmolar hyperglycemia (4 %), hyperammonemia (n=1) and unknown (n=6).  75 % were alcoholics and 50 % were malnourished with albumen mean 2.6.  Half were chronically hypertensive, one third were taking diuretics, 17 % had DM and 1 had ahad liver-kidney transplant.  Forty percent of hyponatremic patients also were hypokalemic, and mean nadir of Na was 114.

4. Presentations included encephalopathy (75 %), ataxia (46 %), dysarthria (29 %), eom abnormalities (25 %), seizures (21 %), eps including chorea. 

5.  Initial MRI was negative in 5 patients and became positive later.

6.  Four of 14 patients so tested had Gd+ lesion on MRI

7.  Ten of 24 patients achieved favorable outcome (mRS<2) at discharge, 15/24 were favorable at 22 months. 

8.  Many patients did not have prior IWMD

Tuesday, November 29, 2011

Treximet v. Fiorecet favors the industry over the generic

Sumatriptan-Naproxen and Butalbital: A Double-Blind, Placebo-Controlled Crossover Study; Derosier F, Sheftell F, Silberstein S, Cady R, Ruoff G, Krishen A, Peykamian M; Headache (Nov 2011)

Objectives.- The primary objective was to compare the efficacy of a sumatriptan and naproxen combination medication (SumaRT/Nap-85 mg sumatriptan and 500 mg naproxen sodium), a butalbital-containing combination medication (BCM-50 mg butalbital, 325 mg acetaminophen, 40 mg caffeine), and placebo when used to treat moderate to severe migraine headache pain in subjects who used BCMs in the past. Background.- Despite the lack of Food and Drug Administration approval and the absence of placebo-controlled trials to demonstrate efficacy, butalbital-containing medications are among the most commonly prescribed acute migraine treatments in the United States. Butalbital-containing medications are associated with serious and undesirable side effects, and have been linked to the chronification of migraine and development of medication-overuse headaches. This study compares the relative efficacy, safety, and tolerability of a fixed dose SumaRT/Nap versus a BCM and placebo. Methods.- Enrolled subjects were required to have treated at least 1 migraine with a butalbital medication in the past. Enrolled subjects treated 3 moderate to severe migraines using each of the 3 study treatments once in a randomized sequence. The primary endpoint compared SumaRT/Nap versus BCM for sustained pain freedom at 2-24 hours without the use of any rescue medication. This study combines data from 2 identical outpatient, randomized, multicenter, double-blind, double-dummy, 3 attack crossover studies in adult migraineurs (International Classification of Headache Disorders, 2nd edition). Results.- A total of 442 subjects treated at least 1 attack with study medication. The majority of the treated subjects were female (88%) with a mean age 43 years, who reported that their migraines had a severe impact on their lives (78% with Headache Impact Test-6 of>59). At screening, 88% of subjects reported current butalbital use; 68% had used butalbital for more than 6 weeks; and 82% reported satisfaction with butalbital. Across treatment groups, 28-29% of subjects took study medication within 15 minutes of migraine onset, 34-37% of subjects took study medication>15 minutes to 2 hours after onset, and 32-36% of subjects took study medication more than 2 hours after onset. This study did not detect a difference at the nominal 0.05 level in percent sustained pain-free between SumaRT/Nap (8%), BCM (6%), and placebo (3%). SumaRT/Nap was superior to BCM for pain free at 2, 4, 6, 8, 24, 48 hours (P ≤ .044); pain relief (mild or no pain) at 2, 4, 6, 8, 24, 48 hours (P ≤ .01); sustained pain relief 2-24 hours (P < .001); migraine free (pain free with no nausea, photophobia, or phonophobia) at 4, 6, 8, 24, 48 hours (P ≤ .046); and complete symptom free (migraine free with no neck/sinus pain) at 4, 6, 8, 48 hours (P ≤ .031). Adverse event incidence was similar for all treatments (10%, 12%, and 9% for placebo, SumaRT/Nap, and BCM, respectively). Nausea was the most frequent adverse event (2%, 2%, and<1% for placebo, SumaRT/Nap, and BCM, respectively). Five serious adverse events were reported by 3 subjects: viral meningitis and colon neoplasm (placebo); chest pain and hypertension 17 days postdose (SumaRT/Nap); and breast cancer (BCM). Investigators judged no serious adverse events related to study medication. Conclusions.- This study primarily included subjects whose migraines significantly impacted their lives. Before the study, these subjects used butalbital-containing medications as part of their current migraine treatment regimen and were satisfied with it, suggesting they were butalbital responders who had found a workable treatment strategy for themselves. When treated with SumaRT/Nap versus BCM in this study, however, a significant proportion of subjects reported better treatment outcomes for themselves for both migraine pain and associated symptoms. Use of SumaRT/Nap was also associated with less rescue medication use and a longer time before use of rescue medication compared with both BCM and placebo.


Blogger note: this is an interesting study, but begs the question that the most common reason neurologists prescribe fiorecet is that the patient is considered unsafe to receive triptans for various reasons. 


Ketamine: to induce coma in cases of brain injury?

BET 3: Is ketamine a viable induction agent for the trauma patient with potential brain injury; Emergency Medicine Journal 28 (12), 1076-7 (Dec 2011)

A short cut review was carried out to establish whether ketamine is a viable induction agent in trauma patients with potential brain injuries. 276 papers were found using the reported searches, of which 5 presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. It is concluded that there is no evidence to suggest harm with Ketamine use as induction agent for the patient with potential traumatic brain injury. The drug has major advantages in those patients with associated haemodynamic compromise and should potentially be regarded as the agent of choice.


Blogger note:  Always beware when a meta-analysis tries to answer questions not posed by the papers meta-analyzed.  As always, the devil is in the details.

Skull based osteomyelitis

Skull base osteomyelitis]; Benoudiba F, Toulgoat F, Sarrazin JL; Journal de Radiologie 92 (11), 987-94 (Nov 2011)

Skull base osteomyelitis is a rare but serious infection. It typically afflicts immunosuppressed patients and should be suspected in patients with persistent otitis complicated by cranial nerve palsy (VII, IX and XII). The most frequent germ is pseudomonas aeruginosa. Contiguous spread of infection occurs along neurovascular structures and weaker regions of the skull base, then into the soft tissue compartments of the face and nasopharynx. Diagnosis and treatment should be made early for this disease with poor prognosis and high mortality.


Blogger note:  Hopefully neurologists won't miss that there is something wrong when they examine this patient, but in case they forget, the germ to treat is pseudomonas.

Saturday, August 20, 2011

the fourteen review of systems are.... (drumroll)

I hate to waste my few remaining neurons on memorizing this but its clear that failure to document will cost not one but two levels of reimbursement (and no one cannot attest in aggregate " a fourteen point ROS was done and was negative") and one cannot make up your own 14 ROS or state there are 17 or 35 there are only 14 defined by PAYORS (no matter how retarded the categories) here they are
1.  General/Constitutional
2.  Eyes
3.  ENT
4.  Heart/CV
5.  Respiratory
6.  GIT
7.  GU
8.  Musculoskeletal
9.  Neurologic
11. Psychiatric
12. All/immunologic
13. Skin
14.  Endocrine
Health screening

Saturday, July 09, 2011

prolonged visit codes

Must document time for all of these codes
code 99354 extended care code for outpatients first hour
99356/99357  extended care for inpatients
Consider using if you are doing a prolonged consult on someone who has been seen in last 3 years, not eligible for new patient code.  If took 1  hour 15 minutes, bill at highest level established patient (99215) for first forty minutes, and 99354 for subsequent face to face time .  Over 74 minutes can use additional code for time. 
IF ARNP sees patient first (CE) then MD sees or vice versa.
99239 code for discharge codes more than 30 minutes. 
Critical care 99291/'99292 first hour (31-74 minutes for 99291 and 99292 for each subsequent half hour). Tpa good choice, add all your time together. document time.Includes time with radiologist, time on unit. 
Use modifier 25 for LP if done on same day as E and M service.

Saturday, June 11, 2011

Lamotrigine in pregnancy and absent major malformations

Cunningham MC et al.  Final results from 18 years of the Lamotrigine Pregnancy Registry.  Neurology 2011; 76: 1817-1823. 

1558 first trimester exposures occurred.  There were 35 infants (2.2 %) with major congenital malformations.  This is similar to population based cohorts.  However, the number was 10.7%ammmong the 150 exposed both to lamotrigine and valproate in the first trimester and 2.8 % in 430 patients exposed to lamotrigine polytherapy without valproate.  Among patients with first trimester monopharmacy with lamotrigine, there were 3 cases of anencephaly, all of which were electively terminated.

Postictal wandering localizes to temporal> extratemporal focus

Tai P. et al.  Postictal wandering (PIW) is common after temporal lobe seizures.  Neurology 2010; 74:11:924-931.

PIW occurs in 4 % of seizures, and 13 % of seizures of patients who experienced PIW (n=42 patients admitted to an epilepsy monitoring unit in Toronto.  It occurred in 9/20 with TLE and 2/22 with non TLE, and 18/186 temporal seizures, and 2/266 non temporal lobe seizures.

Literature tends to emphasize frontal seizures, contrary to these results, but may reflect selection bias of a different group. 

Cryptococcosis in non-immunosuppressed

Bestard J, Siddiqi ZA.  Cryptococcal meningoencephalitis in immunocompetent patients: changing trends in Canada.  Neurology 74:15 April 13, 2010 pp 1233-1234

Cryptococcus neoformans have 3 subtypes :  var grubii and var neoformans affect immunosuppressed, whereas CN var gatii affects non-immunosuppressed, especially males.  Its found in decaying heartwood of decaying tree species in tropics and also Vancouver Island, exclusively in British Columbia. 

Monday, April 25, 2011

Flail arm and flail leg variants of ALS

Neurology 2009; 72: 1087-1094

These are phenotypic variants of ALS that have been described a century or more ago that have unique characteristics including

1.  In flail arm, proximal wasting and weakness, in flail leg, distal weakness or wasting
2.  LMN variant with no clonus, hypertonia or UMN signs, or involvement of other extremity (leg +  arm) or bulbar involvement
3.  4:1 male predominance in FA, 1:1 gender equality in FL in London; 10:1 and 5:1 respectively in Melbourne series
4.  Relatively longer prognosis than other forms of ALS with lifespan of around 6 years

Synonyms FA:  Vulpian-Bernhardt syndrome, hanging arm syndrome, neurogenic man in a barrel syndrome, or amyotrophic brachial diplegia
Synonyms FL: Marie -Patrikios variant, pseudopolyneuritic variant of ALS, peroneal form of ALS

Delayed cerebral thrombosis after initial good recovery from pc meningitis

Schut ES, Brouwer MC, de Gan J, Florquin S, et al.  Neurology 2009; 73: 1988-1995.

Dutch authors have small case series of patients who recovered apparently from meningitis then developed stroke on a delayed basis 2-3 weeks after recovery.  6 patients, including 5 males 30-73 got dexamethasone for pneumococcal meningitis.  After 7-19 days  patients suddenly deteriorated with headache, fever, loss of consciousness, brainstem signs and had thalamic or brainstem strokes in penetrating artery territory.  LP's were sterile. 
In discussion, authors note they surveyed a similar population in the predexamethasone days and found no delayed strokes.  Authors speculate that withdrawing corticosteroids may be compromising and suggest reinstating high dose steroids in these patients, as well repeating LP promptly, treating with antibiotics again, and checking for endocarditis.

Saturday, April 23, 2011

treatment of photosensitive seizures

Take Home Points
• Light-induced seizures are not uncommon.
• Most patient with epilepsy can safely watch
television or play video games (using easy
preventive measures in those who are lightsensitive).
• Blue sunglasses can be very effective (and
documented with EEG & photic stimulation).
• Valproate & levetiracetam are the two most
effective treatments currently available, and the
drug selection for a given epilepsy syndrome
should consider if photosensitivity is present.
• Follow-up EEG with photic stimulation is helpful to
access the patient's response to treatment.

photosensitive seizures

• 4.1 to 8.9% prevalence of photosensitivity
(without other seizures) in population
- 49% television induced
- 43% video game induced
• 76% of children with photosensitive
seizures to Pokemon had never had a prior
seizure, and 90% of these did not go on to
develop seizures.
• Broadcasting guidelines have dramatically
decreased photosensitive seizures
Takahashi Y et al. Neurology, 2004; 62: 990-993.

Epilepsy Syndromes Associatedwith Photosensitivity

Epilepsy Syndromes Associated
with Photosensitivity

– Benign myoclonic epilepsy in infancy
– Severe myoclonic epilepsy of infancy (Dravet Syndrome)
– Myoclonic-astatic epilepsy (Doose Syndrome)
– Childhood absence & juvenile absence (13-18%)
– Juvenile myoclonic epilepsy (30-35%)
– Epilepsy with GTC seizures on awakening (13%)
– Primary reading epilepsy (<10%)
– Jeavons syndrome (eyelid myoclonia and absences)
– Progressive myoclonic epilepsies (NCLFs, Lafora's
disease, Unverricht-Lundborg disease, MERRF)
– Idiopathic photosensitive occipital lobe epilepsy.
Guerrini R, Genton P. Epilepsia, 2004; 45 (Suppl 1): 14-18.
Photosensitivity: Types of
Seizures Induced
• Prevalence based on the literature:
– GTC (55-84%)
– Absences (6-20%)
– Myoclonic jerks (2-8%)
– Focal seizures (2.5%)
• Reports may over-exaggerate GTCs in
relation to "minor" seizure events.
• Clinical experience: Myoclonic jerks >
absences > GTCs.
Panayiotopoulos C. Epileptic Syndromes and Their Treatment. Springer. London 2009.
Photosensitivity Historical Timeline
1885 Gowers described girl with seizures when going into
bright sunlight
1932 Radovici described eyelid myoclonias and absence
seizures in response to eyelid closure while looking
at bright light
1952 Livingston reported TV-induced seizures for 1st time
1962 Gastaut studied 35 patients with TV induced
1981 Rushton reports "Space-Invader epilepsy"
1993 TV commercial caused 3 seizures in UK. Guidelines
for photic stimulation in commercials introduced.
1997 Pokemon Episode (Pikachu) induced seizures in
560 Japanese children.

Aggravation of Severe Myoclonic Epilepsy (SMEI) by Lamotrigine

v Twenty-one SMEI patients (age 2-18 years, mean
9 years)

v Convulsive seizures increased by >50% in 8 of 20
pts, myoclonic seizures worsened in 6 of 18 pts.

v Of 5 pts with improvement in one seizure type, 4
had concomitant worsening of more disabling

v Lamotrigine was withdrawn in 19 pts, with
consequent improvement in 18
R. Guerrini et al, Epilepsia 1998;39, 508-12

myoclonus fromgabapentin

Myoclonus Associated with the Use of Gabapentin

v Of 104 consecutive patients treated with
gabapentin, 13 (12.5%) developed myoclonus
v All patients (age 14 to 41 years) had refractory
partial epilepsy, 6 had a static encephalopathy
v Myoclonus was multifocal in 10, contralateral to
the epilepticus focus in 3
v Myoclonus persisted for as long as gabapentin
was continued. Disappeared on drug withdrawal.
v An EEG recording in 3 patients showed no
J. Asconapé et al., Epilepsia 2000:41:479-82

Thursday, February 17, 2011

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.