BCGP / Neurology

Answer: C If patient is seizure-free for 3-5 years, it is OK to gradually taper down over a minimum of month time period. It should never be abruptly discontinued due to increased risk of relapse. It is optimal to decrease dose to 200mg daily for a month, then to 100 mg daily for a month before discontinuing it.
Reference:
Ranganathan, L, Ramaratnam, S.Rapid versus slow withdrawal of antiepileptic drugs.Cochrane Database Syst Rev. 2006 Apr 19;(2): CD005003. https://www.ncbi.nlm.nih.gov/pubmed/16625621.

Answer: C Valproic acid has the following black box warning: life-threatening pancreatitis reported in both children and adults receiving valproate. Sometimes described as hemorrhagic with rapid progression from initial symptoms to death. Cases have been reported after initial use as well as after several years of use.
Reference:
Jones, M, et al. Drug-induced acute pancreatitis: a review. Ochsner J. 2015 Spring;15(1):45-51. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365846/.

Answer: D It is important to monitor liver functions tests plasma ammonia levels in patients on divalproex sodium.1 It is also imperative that complete blood counts coagulation tests are assessed as well.2
Reference:
1.DEPAKENE oral capsules, oral solution, valproic acid oral capsules, oral solution. AbbVie Inc. (per FDA) , North Chicago, IL, 2014.

Answer: C Topiramate is a weak carbonic anhydrase inhibitor that increases urinary pH and reduces urinary citrate excretion ultimately promoting kidney stone formation .
Reference:
Topamax (topiramate) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals Inc; April 2014.

Answer: C Dose-dependent hyperammonemia usually occurs when topiramate is taken in combination with valproic acid, but it can also occur with topiramate monotherapy
Reference:
Topamax (topiramate) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals Inc; April 2014.

Answer A. Dose related Syndrome of Inappropriate Antidiuretic Hormone (SIADH) occurs with carbamazepine.
Reference:
Carbamazepine [prescribing information]. North Wales, PA: Teva; September 2014.

Answer C. There is a black box warning for a serious hypersensitivity reaction that manifests as a rash in patients who take lamotrigine, therefore it’s important to start at the lowest dose possible and slowly increase the dose to decrease the likelihood of the reactions occurring.
Reference:
Kanner, A. Lamotrigine-induced Rash: Can We Stop Worrying? Epilepsy Curr. 2005 Sep; 5(5): 190–191. doi:10.1111/j.1535-7511.2005.00060.x. http://onlinelibrary.wiley.com/doi/10.1111/j.1535-7511.2005.00060.x/abstract.

Answer B. According to the manufacturer, the following additional adverse reactions have been reported: Hemopoietic System: Aplastic anemia, agranulocytosis, pancytopenia, bone marrow depression, thrombocytopenia, leukopenia, leukocytosis, eosinophilia, acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda.
Reference:
Tegretol. [package insert]. East Hanover, NJ. Novartis Pharmaceuticals Corporation. Sept 2015.

Answer A. There is a strong relationship between HLA-B*1502 and carbamazepine-induced SJS and TEN in Han-Chinese, Thai, and Malaysian populations.1 This same relationship and between HLA*1502 and SJS/TEN has been also found with phenytoin and lamotrigine.
Reference:
1. Tangamornsuksan, W, Chaiyakunapruk, N, et al. Relationship between the HLA-B*1502 allele and carbamazepine-induced stevens-johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. JAMA Dermatol. 2013;149(9):1025-1032. doi:10.1001/jamadermatol.2013.4114.
2. Li, X, Yu, K, et al. HLA-B*1502 increases risk of phenytoin or lamotrigine induced stevens-johnson syndrome/toxic epidermal necrolysis: evidence from a meta-analysis of nine case-control studies. Drug Res (Stuttg). 2015 Feb;65(2):107-11. doi: 10.1055/s-0034-1375684. Epub 2014 May 28.https://www.ncbi.nlm.nih.gov/pubmed/24871931.

Answer D. According to medwatch, the FDA Safety Information and Adverse Event Reporting System, there have been reports in clinical trials with patients having increased P-R interval while taking lacosamide. EKG monitoring is recommended.
Reference:
Department of Health and Human Services. U.S. Food and Drug Administration. Available at:https://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm342620.htm. Published February 2013. Accessed March 8, 2017.

Answer A. Rivastigmine and galantamine are FDA approved for mild to moderate Alzheimer’s dementia. Memantine is FDA approved specifically for moderate to severe Alzheimer’s dementia but it is an NMDA antagonist and not an acetylcholinesterase Inhibitor. Donepezil is the only FDA approved acetylcholinesterase Inhibitor for use in severe dementia (mild-moderate).
Reference:
Rabins P, Rovner B, Rummans T, Schneider L, Tariot P. Guideline Watch (October 2014): Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias. FOCUS. 2017;15(1):110-128. doi:10.1176/appi.focus.15106.

Answer C. 1.5 mg of fosphenytoin is equivalent to 1 mg of phenytoin equivalents (150 mg of fosphenytoin for 100 mg of phenytoin equivalent).
Reference:
Millares-Sipin, C, Alafris, A, et al.Phenytoin and Fosphenytoin. In: Cohen H. Cohen H Ed. Henry Cohen.eds. Casebook in Clinical Pharmacokinetics and Drug Dosing New York, NY: McGraw-Hill

AnswerD. If CRCL < 20 mL/min then Corrected Phenytoin
Corrected phenytoin = Total phenytoin Level / ((0.1 x albumin) + 0.1)
= 10.8/(0.1x2.1) + 0.1
= 34.8mcg/mL
Reference:
Wu, M, Lim, W. Phenytoin: A Guide to Therapeutic Drug Monitoring. Proceedings of Singapore Healthcare. 22 (3):198-202. 2013. Available at: http://journals.sagepub.com/doi/pdf/10.1177/201010581302200307. Accessed March 8, 2017.

Answer B. When Asians have the HLA-B*1502 allele, and they take phenytoin, they are at increased risk of Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The same concern is applicable to the prodrug of phenytoin, fosphenytoin.
Reference:
U.S. Department of Health and Human Services. Information for Healthcare Professionals: Phenytoin (marketed as Dilantin, Phenytek and generics) and Fosphenytoin Sodium (marketed as Cerebyx and generics). Food and Drug Administration. Updated Aug 2013. Available at: https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124788.htm .

Answer A. Non dose-related side effects of phenytoin include: Gingival hyperplasia, hirsutism, thickening of facial features, vitamin D deficiency, folic acid deficiency, osteomalacia, peripheral neuropathy.
Reference:
Faye Wu, M, Hing Lim W. Phenytoin: a guide to therapeutic drug monitoring. Proceedings of Singapore Healthcare. 2013. 22 (3). Accessed Mar 8 2017. Available at: http://journals.sagepub.com/doi/pdf/10.1177/201010581302200307.

Answer D. Common dose-related side effects of phenytoin include: Central nervous system effects: somnolence, fatigue, dizziness,confusion, visual disturbances, nystagmus and ataxia.
Reference:
Faye Wu, M, Hing Lim W. Phenytoin: a guide to therapeutic drug monitoring. Proceedings of Singapore Healthcare. 2013. 22 (3). Accessed Mar 8 2017. Available at: http://journals.sagepub.com/doi/pdf/10.1177/201010581302200307.

Answer D. Acetylcholinesterase inhibitors prevent the degradation of acetylcholine enhancing its binding with receptors. Acetylcholine stimulates salivation. A patient would experience dry mouth from an anti-cholinergic medication but not an acetylcholinesterase inhibitor.
Reference:
Rivastigmine tartrate capsule [package insert]. Cranbury, NJ: Sun Pharmaceutical Industried Ltd; 2016

Answer B. Donepezil and galantamine have been used off label for Parkinson’s disease dementia but only rivastigmine is FDA approved for the indication.
Reference:
Exelon New FDA Drug Approval | CenterWatch. Centerwatchcom. 2017. Available at: http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/957/exelon-rivastigmine-tartrate Accessed August 22, 2017.

Answer C. Long term use of acetylcholinesterase inhibitors has been associated with anorexia, weight loss, falls, hip fractures, syncope, bradycardia, and increased use of cardiac pacemakers.
Reference:
Rabins P, Rovner B, Rummans T, Schneider L, Tariot P. Guideline Watch (October 2014): Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias. FOCUS. 2017;15(1):110-128. doi:10.1176/appi.focus.15106.

Answer D. Mini Mental Status Examination (MMSE) has three categories for dementia: a score of 20-24 is mild dementia, 13-20 is moderate dementia, and less than 12 is severe dementia. Because the patient’s MMSE score is lower her dementia is worsening. Decreasing her dose to 3 mg BID with signs of worsening cognition and the absence of side effects would not be appropriate. Donepezil is in the same class of rivastigmine and would increase the risk of side effects. The maximum dose of rivastigmine is 12 mg/day orally making 8 mg BID inappropriate. Memantine can be used with acetylcholinesterase Inhibitors and would be an appropriate supplementation to rivastigmine as the patient’s cognitive function continues to decline.
Reference:
I. Tests for Alzheimer's & Dementia | Alzheimer's Association. Alzorg. 2017. Available at: http://www.alz.org/alzheimers_disease_steps_to_diagnosis.asp#mmse . Accessed August 22, 2017.
II. Rivastigmine tartrate capsule [package insert]. Cranbury, NJ: Sun Pharmaceutical Industried Ltd; 2016
III. Rabins P, Rovner B, Rummans T, Schneider L, Tariot P. Guideline Watch (October 2014): Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias. FOCUS. 2017;15(1):110-128. doi:10.1176/appi.focus.15106.

Answer A. Both atypical and typical antipsychotics have been associated with increased risk of death in elderly patients treated for dementia-related psychosis. This caused the FDA to issue a black box warning for both classes to alert health care providers.
Reference:
I. Information for Healthcare Professionals: Conventional Antipsychotics. Fdagov. 2017. Available at: https://www.fda.gov/Drugs/DrugSafety/ucm124830.htm . Accessed August 22, 2017.
II. Rabins P, Rovner B, Rummans T, Schneider L, Tariot P. Guideline Watch (October 2014): Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias. FOCUS. 2017;15(1):110-128. doi:10.1176/appi.focus.15106.

Answer A. Patients treated in the olanzapine group experienced a worsening of functional skills compared to placebo. Patients assigned to receive antipsychotics for psychosis or agitated behavior did not demonstrate a significant improvement in cognitions, care needs, or quality of life compared to placebo.
Reference:
Sultzer D, Davis S, Tariot P et al. Clinical Symptom Responses to Atypical Antipsychotic Medications in Alzheimer’s Disease: Phase 1 Outcomes From the CATIE-AD Effectiveness Trial. American Journal of Psychiatry. 2008;165(7):844-854. doi:10.1176/appi.ajp.2008.07111779.

A literature review of management of MS exacerbation treatments concluded that IV steroids are the preferred route of administration. High doses of IV methylprednisolone varying from 500 to 1000 mg for 3-5 days has been found to be effective. Oral steroid tapers have no supporting evidence. Reference: Rae-Grant A, Ontaneda D. Management of acute exacerbations in multiple sclerosis. Ann Indian Acad Neurol. 2009;12(4):264. doi:10.4103/0972-2327.58283

Answer: E At present, no therapy can slow down or arrest the progression of Parkinson's disease, however, emerging therapies exist and are currently being examined in clinical studies. Such research includes vaccines, neuroinflammatory therapies, diets and microbiome, cannabinoids, gene therapy, and next generation adaptive deep brain tissue stimulation.
Reference:
Bloem BR, Okun MS, Klein C. Parkinson's disease. Lancet. 2021 Jun 12;397(10291):2284-2303. doi: 10.1016/S0140-6736(21)00218-X. Epub 2021 Apr 10. PMID: 33848468.

Answer: C, E – Resting tremor, bradykinesia, and rigidity are all motor symptoms of Parkinson’s disease since they are correlated to the reduction of movement, or limited range of movement. Sialorrhea, or hypersalivation is a non-motor symptom since it is not associated to reduction in motor function but is known to occur later on in the disease course of patients with Parkinson’s disease. Tardive dyskinesia is a condition affecting the nervous system often caused by a long term use of antipsychotics such as olanzapine, risperidone, quetiapine. Tardive dyskinesia causes uncontrollable stiff, jerky movement of face and body.
Reference:
Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson disease. Arch Neurol. 1999 Jan;56(1):33-9. doi: 10.1001/archneur.56.1.33. PMID: 9923759.

Answer: A – Carbidopa/levodopa 12.5-50mg or Carbidopa/levodopa 25-100 mg – Levodopa treatment has been shown to be associated with greater motor movement improvements than other approved therapy, however it has been shown to have greater risk of dyskinesia following prolonged use and patients will become progressively resistant to treatment over time, despite initial beneficial response. One argument to postpone treatment is the long-held notion that levodopa could be toxic and hasten disease progression by promoting oxidative stress, fueling levodopa phobia and motivating both physicians and people with Parkinson's disease to postpone treatment. However, in the LEAP study, which used a delayed start design in which people with Parkinson's disease either received levodopa immediately, or after a placebo period of 9 months, showed no evidence of levodopa toxicity, or for neuroprotective effects. However, early starters manifested fewer motor symptoms and had a better quality of life than the late starters. Moreover, observations in African people with Parkinson's disease, who postponed medication due to a scarcity of access, revealed that delaying treatment did not reduce the likelihood of motor complications and dyskinesias. The consensus is that there is no rationale to postpone symptomatic treatment in people with Parkinson's disease who develop a disability
Reference:
Verschuur CVM, Suwijn SR, Boel JA, Post B, Bloem BR, van Hilten JJ, van Laar T, Tissingh G, Munts AG, Deuschl G, Lang AE, Dijkgraaf MGW, de Haan RJ, de Bie RMA; LEAP Study Group. Randomized Delayed-Start Trial of Levodopa in Parkinson's Disease. N Engl J Med. 2019 Jan 24;380(4):315-324. doi: 10.1056/NEJMoa1809983. PMID: 30673543. Bloem BR, Okun MS, Klein C. Parkinson's disease. Lancet. 2021 Jun 12;397(10291):2284-2303. doi: 10.1016/S0140-6736(21)00218-X. Epub 2021 Apr 10. PMID: 33848468. Cilia R, Akpalu A, Sarfo FS, Cham M, Amboni M, Cereda E, Fabbri M, Adjei P, Akassi J, Bonetti A, Pezzoli G. The modern pre-levodopa era of Parkinson's disease: insights into motor complications from sub-Saharan Africa. Brain. 2014 Oct;137(Pt 10):2731-42. doi: 10.1093/brain/awu195. Epub 2014 Jul 17. PMID: 25034897; PMCID: PMC4163032.

Answer: B – Dopamine agonists cause side effects such as sudden sleep attacks and impulsive control disorders; gambling, hyper-sexual behaviors, and excessive shopping can occur while taking these agents. Ropinirole is the only dopamine agonist on the list.
Reference:
Diagnosis and prognosis of new onset of Parkinson disease; an evidence based review. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006. April 11;66(7):968-975.
Bloem BR, Okun MS, Klein C. Parkinson's disease. Lancet. 2021 Jun 12;397(10291):2284-2303. doi: 10.1016/S0140-6736(21)00218-X. Epub 2021 Apr 10. PMID: 33848468.

Answer: B - Dopamine agonists cause side effects such as sudden sleep attacks and impulsive control disorders; gambling, hyper-sexual behaviors, and excessive shopping can occur while taking these agents. Pramipexole is the only dopamine agonist on the list.
Reference:
Diagnosis and prognosis of new onset of Parkinson disease; an evidence based review. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006. April 11;66(7):968-975.
Bloem BR, Okun MS, Klein C. Parkinson's disease. Lancet. 2021 Jun 12;397(10291):2284-2303. doi: 10.1016/S0140-6736(21)00218-X. Epub 2021 Apr 10. PMID: 33848468.

Answer: A, B, C – Periods of “off time” can occur in patients who are on an adequate treatment for PD. The “off time” is described as a worsening of parkinsonian symptoms before the next doses of medications are due; muscle stiffness, slow movements, and difficulty starting movements are commonly seen in patients who are experiencing “off time”. Adding on a dopamine agonist medication, adding on a COMTI/MAOBI, increasing doses of dopaminergic medications, and giving dopaminergic medications more frequently but with higher doses are some of the strategies to reduce the “off time” seen in patients with managed PD therapy.
Reference:
Pharmacological Treatment of Parkinson’s Disease, A Review. Journal of American Medical Association. 2014. April 23;311(16): 1670-1683.
Bloem BR, Okun MS, Klein C. Parkinson's disease. Lancet. 2021 Jun 12;397(10291):2284-2303. doi: 10.1016/S0140-6736(21)00218-X. Epub 2021 Apr 10. PMID: 33848468

Answer: B – Levodopa is primarily responsible for dyskinesias, therefore, decreasing dose of carbidopa/levodopa will decrease the involuntary movements the patient is experiencing, since there will be less of levodopa in patient’s system. However, reduction of carbidopa/levodopa dose may lead to worsening of parkinsonism symptoms. First-line treatment strategies include lowering the dose of levodopa and/or adjunctive dopaminergic therapies, when possible, and use of a medication to help suppress dyskinesia, such as amantadine (dopamine agonist) or clozapine (second generation antipsychotic).
Reference:
Diagnosis and prognosis of new onset of Parkinson disease; an evidence based review. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006. April 11;66(7):968-975.
Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review. JAMA. 2014 Apr 23-30;311(16):1670-83. doi: 10.1001/jama.2014.3654. PMID: 24756517.

Answer: A – The patient is exhibiting symptoms of dyskinesia. Peak-dose or "on" dyskinesia can occur in any patient with PD if the levodopa dose is high enough, typically starting 30 to 90 minutes after a dose. Although dyskinesia can sometimes be reversed, the condition is permanent in the majority of people. First-line treatment strategies include lowering the dose of levodopa and/or adjunctive dopaminergic therapies, when possible, and use of a medication to help suppress dyskinesia, such as amantadine (dopamine agonist) or clozapine (second generation antipsychotic).
Reference:
Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review. JAMA. 2014 Apr 23-30;311(16):1670-83. doi: 10.1001/jama.2014.3654. PMID: 24756517.
Pahwa R, Factor SA, Lyons KE, Ondo WG, Gronseth G, Bronte-Stewart H, Hallett M, Miyasaki J, Stevens J, Weiner WJ; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):983-95. doi: 10.1212/01.wnl.0000215250.82576.87. PMID: 16606909.

Since benztropine is an anticholinergic drug, and amantadine has anticholinergic effects, both amantadine and benztropine can lead to hallucinations, dry mouth, blurred vision, and constipation - common anticholinergic side effects.
Reference:
Pharmacological Treatment of Parkinson’s Disease, A Review. Journal of American Medical Association. 2014. April 23;311(16): 1670-1683.
Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med. 2008 Mar 10;168(5):508-13. doi: 10.1001/archinternmed.2007.106. PMID: 18332297.

Answer: D – Amantadine is one of the most common drugs that can lead to livedo reticularis, a reversible side effect that presents as an erythematous-cyanotic well defined spots. After the condition appears on the skin, it has a variable clinical course ranging between 1 and 48 months. Discontinuation of medication is necessary to resolve this condition.
Reference:
Amantadine-Induced Livedo Reticularis – A Case Report. Anais Brasileiros De Dermatologia. 2015. September; 90(5): 745-747. Amantadine hydrochloride capsules [prescribing information]. Bridgewater, NJ: Alembic Pharmaceuticals, Inc; April 2017.
Quaresma MV, Gomes AC, Serruya A, Vendramini DL, Braga L, Buçard AM. Amantadine-induced livedo reticularis--Case report. An Bras Dermatol. 2015 Sep-Oct;90(5):745-7. doi: 10.1590/abd1806-4841.20153394. PMID: 26560223; PMCID: PMC4631243.

Answer: A,B,D– Orthostatic hypotension can occur due to the anatomic dysfunction with PD, or it may be a side effect of dopaminergic medications. Amantadine, pramipexole, and carbidopa/levodopa have orthostatic hypotension as a listed adverse effect in their package insert.
Reference:
Pharmacological Treatment of Parkinson’s Disease, A Review. Journal of American Medical Association. 2014. April 23;311(16): 1670-1683.

Answer: A. Metoclopramide, prochlorperazine, and promethazine worsen parkinsonian symptoms and should be avoided. Serotonin antagonist, ondansetron can lead to severe hypotension and loss of consciousness when given with apomorphine, and should therefore be avoided to treat nausea associated with use of apomorphine. Nausea caused by all other dopaminergic agents should be treated with ondansetron or domperidone.
Reference:
Pharmacological Treatment of Parkinson’s Disease, A Review. Journal of American Medical Association. 2014. April 23;311(16): 1670-1683.

Answer: E - Hallucinations can be a feature of later stages of PD, or they could occur due to use of medications that treat the disease; since the patient realizes the hallucinations are not real, and he denies associated distress due to hallucinations the pharmacological therapy is not indicated. If the hallucinations become increased in intensity or become troublesome for the patient, decrease or discontinuation of antiparkinsonian drugs, or initiation of clozapine or quetiapine can help combat the hallucinations.
Reference:
Pharmacological Treatment of Parkinson’s Disease, A Review. Journal of American Medical Association. 2014. April 23;311(16): 1670-1683.

Answer: D – Midodrine, Yohimbine, and fludrocortisone are all used in treatment of orthostatic hypotension that can occur in PD. Although fludrocortisone has most evidence supporting its use, midodrine and Yohimbine can be used to manage orthostatic hypotension as well. Non-pharmacological measures such as increasing salt and fluid consumption, elevating head of the bed, and use of compression stockings should be used in combination with pharmacological agents.
Reference:
Pharmacological Treatment of Parkinson’s Disease, A Review. Journal of American Medical Association. 2014. April 23;311(16): 1670-1683.
Palma JA, Kaufmann H. Orthostatic Hypotension in Parkinson Disease. Clin Geriatr Med. 2020;36(1):53-67. doi:10.1016/j.cger.2019.09.002

Answer: E – clonazepam is the medication of choice for treatment of Rapid Eye Movement Sleep Behavior Disorder in patients with Parkinson’s Disease. Melatonin is given to patients who do not tolerate the treatment with clonazepam, or patients with contraindications to clonazepam use.
Reference:
Pharmacological Treatment of Parkinson’s Disease, A Review. Journal of American Medical Association. 2014. April 23;311(16): 1670-1683.
Olson EJ, Boeve BF, Silber MH. Rapid eye movement sleep behaviour disorder: demographic, clinical and laboratory findings in 93 cases. Brain. 2000;123(pt 2):331‐339. doi:10.1093/brain/123.2.331[PubMed 10648440]

A literature review of management of MS exacerbation treatments concluded that IV steroids are the preferred route of administration. High doses of IV methylprednisolone varying from 500 to 1000 mg for 3-5 days has been found to be effective. Oral steroid tapers have no supporting evidence. Reference: Rae-Grant A, Ontaneda D. Management of acute exacerbations in multiple sclerosis. Ann Indian Acad Neurol. 2009;12(4):264. doi:10.4103/0972-2327.58283