Cancer Treatment Today » Neurology

Rituxan for Opsoclonus Myoclonus Syndrome – pro

M Levin, MD — Wed, 10 Oct 2012 18:43:16 +0000

Rituxan has been reported to alleviate the myoclonus opsoclonus syndrome in case reports and series. Presumably there is an immunologic mechanism underlying this observation. Approximately 50 % of patients with OMS have an associated neuroblastoma or associated infections have also been reported. There is no specific diagnostic biomarker for OMS. Other treatments include as ACTH, corticosteroids, cyclophosphamide and/or intravenous immunoglobulin, develop long-term neurological morbidity. Gordon in a 2011 review concldued that future collaborative studies are needed to determine if early, aggressive therapy will improve the typically poor long-term neurological outcome.

Pranzatelli et al (2010) reported the findings of 12 immunotherapy-naïve children with opsoclonus-myoclonus syndrome (OMS) and cerebrospinal fluid (CSF) B cell expansion who received rituximab, adrenocorticotropic hormone (ACTH), and Iintravenous immunoglobulin. Motor severity lessened 73 % by 6 months and 81 % at 1 year (p < 0.0001). Opsoclonus and action myoclonus disappeared rapidly, whereas gait ataxia and some other motor components improved more slowly. Dosage of ACTH was tapered by 87 %. Reduction in total CSF B cells was profound at 6 months (-93 %). By study end, peripheral B cells returned to 53 % of baseline and serum IgM levels to 63 %. Overall clinical response trailed peripheral B cell and IgM depletion, but improvement continued after their levels recovered. All but 1 non-ambulatory subject became ambulatory without additional chemotherapy; 2 relapsed and remitted; 4 had rituximab-related or possibly related adverse events; and 2 had low-titer human anti-chimeric antibody. The authors concluded that combination of rituximab with conventional agents as initial therapy was effective and safe. They stated that a controlled trial with long-term safety monitoring is indicated.

The proposed treatment is in clinical trials, for example, Use of Rituximab in Opsoclonus-Myoclonus in Children With Neuroblastoma, NCT00202930.

J. K. Sahu et al, The opsoclonus–myoclonus syndrome, Pract Neurol 2011;11:160-166

Gorman MP. Update on diagnosis, treatment, and prognosis in opsoclonus-myoclonus-ataxia syndrome. Curr Opin Pediatr. 2010;22(6):745-750.

Pranzatelli MR, Tate ED, Swan JA, et al. B cell depletion therapy for new-onset opsoclonus-myoclonus. Mov Disord. 2010;25(2):238-242.

For Lay version see Here

The Role of Physical Therapies in Muscular Dystrophies – pro

M Levin, MD — Mon, 20 Aug 2012 18:16:31 +0000

Muscular dystrophy (MD)is a group of genetic diseases that affect muscle function. There are more than 30 genetic mutations that can cause muscular dystrophy. Based on the clinical features, including inheritance pattern, muscles affected, and muscle biopsy features, dystriophis are dvivided into: Duchenne, Becker, Myotonic dystrophy, Facioscapulohumeral, Limb-girdle, Ocullopharyngeal, Congenital and Distal.

Physical therapy, especially regular stretching, is important in helping to maintain the range of motion(ROM) for affected muscles and to prevent or delay contractures. Strengthening less affected muscles to compensate for weakness in the more affected muscles may improve the patient’s ability to engage in activities of daily living(ADL), especially in earlier stages of milder MD. Regular exercise is important in maintaining good overall health, but strenuous exercise should be avoided because it can damage muscles. Age of the patient and degree of dysfunction are not determining criteria of employing physical therapy, as long as an improvement in ROM and ADL can be expected.

Turner, C; Hilton-Jones D. (2010). “The myotonic dystrophies: diagnosis and management”. J Neurol Neurosurg Psychiatry 81: 358–367.

Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C, DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol 2010 Feb;9(2):177-89. [157 references]

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Neuropsychological Testing in Multiple Sclerosis: Importance of Brevity – pro

M Levin, MD — Mon, 06 Aug 2012 14:56:26 +0000

Data shows strong relationships of neuropsychological testing with neuropsychiatric features of the disease, brain imaging and vocational outcomes (1l). Unfortunately, full neuropsychological testing is time consuming and expensive, which limits its usefulness as an ongoing assessment tool. The current tendency is to seek instruments for evaluation which combine diagnostic efficiency, clinical usefulness and brevity. There are current procedures that are found to be more effective evaluation and standard of care for cognition in MS in the literature and yet brief.

Benedict RH, Zivadinov R. Reliability and validity of neuropsychological screening and assessment strategies in MS.J Neurol. 2007 May;254 Suppl 2:II22-II25.

Helmut Hildebrandta, Rogers JM, Panegyres PK.Cognitive training in MS: Effects and relation
to brain atrophyRestorative Neurology and Neuroscience 25 (2007) 33–43 33

Cognitive impairment in multiple sclerosis: evidence-based analysis and recommendations.J Clin Neurosci. 2007 Oct;14(10):919-27.

Pepping M, Ehde DM. Neuropsychological evaluation and treatment of multiple sclerosis: The importance of a neuro-rehabilitation focus. Phys Med Rehabil Clin N Am. 2005;16(2):411-436, viii. Minimal neuropsychological assessment of MS patients: a consensus approach.Clin Neuropsychol. 2002 Aug;16(3):381-97.

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Rituxan in Chronic Demyelinating Polyneuropathy (CDIP) – pro

M Levin, MD — Sun, 05 Aug 2012 14:05:38 +0000

Rituximab is a chimeric monoclonal antibody that targets the CD20 antigen on B lymphocytes. Depletion of B lymphocytes may interfere with antibody-dependent, cell-mediated cytotoxicity involving peripheral nerve. Several recent reports have suggested that rituximab is beneficial in patients with immune-mediated neuropathies.Evidence for Rituxna’s efficacy in CDIP comes mainly from case reports and series and a small placebo controlloed study(Dalakas et al 2009). A recent retrospective study and literature review found that nine patients (seven with haematological diseases) responded to rituximab: six of them, who were non-responders to conventional therapies, improved clinically, and the other three maintained the improvement that they usually achieved with intravenous immunoglobulin or plasma exchange. Significantly associated with shorter disease duration, rituximab responses started after a median period of 2.0 months (range, 1–6) and lasted for a median period of 1 year (range, 1–5). The authors concluded: ” Rituximab seems to be a promising therapeutic choice when it targets both CIDP and co-occurring haematological diseases. Timely post-onset administration of rituximab seems to be associated with better responses.”

However, another recent review(Mnin-Sook) notes the absence of prospective clinical trials and says: “Only three treatment regimens for CIDP have demonstrated benefit in randomized, controlled studies: corticosteroids, plasma exchange, and intravenous immunoglobulins (IVIg). Approximately 25% of patients respond inadequately to corticosteroids, plasma exchange or IVIg. Large placebo-controlled trials with alternative immunosuppressive compounds, e.g. mycophenolate mofetil, cyclosporine, cyclophosphamide, or monoclonal antibodies, are lacking.”

Dalakas MC. Invited article: inhibition of B cell functions: implications for neurology. Neurology. 2008;70(23):2252-60.

Dalakas MC, Rakocevic G, Salajegheh M, Dambrosia JM, Hahn AF, Raju R, McElroy BPlacebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein antibody demyelinating neuropathy.Ann Neurol. 2009 Mar;65(3):286-93.

Münch C, Anagnostou P, Meyer R, Haas J. Rituximab in chronic inflammatory demyelinating polyneuropathy associated with diabetes mellitus.J Neurol Sci. 2007 May 15;256(1-2):100-2.

Kenneth C. Gorson et al, Rituximab treatment in patients with IVIg-dependent immune polyneuropathy: A prospective pilot trial
Muscle & Nerve Volume 35, Issue 1, pages 66–69, January 2007

L Benedetti, Rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a report of 13 cases and review of the literature
J Neurol Neurosurg Psychiatry 2011;82:306-308 doi:10.1136/jnnp.2009.188912

Min-Suk Yoon, Standard and escalating treatment of chronic inflammatory demyelinating polyradiculoneuropathy
Therapeutic Advances in Neurological Disorders May 2011 vol. 4 no. 3 193-200

Transverse Myelitis – pro

M Levin, MD — Sun, 05 Aug 2012 14:03:34 +0000

Transverse myelitis is an inflammatory condition of the spinal cord, which affects thel covering of the nerve cell fibers (myelin). Transverse myelitis causes diminished or absent sensation below the level of the injury injury.

The disrupted transmission of nerve signals due to transverse myelitis can cause pain or other sensory problems, weakness or paralysis of muscles, or bladder and bowel dysfunction. Transverse meylitis has been associated with infections outside the spine, with autoimmune disorders and multiple sclerosis. Treatment for transverse myelitis includes anti-inflammatory drugs, steroids, plasma exchange or immunosupressive drugs and medications to manage symptoms and rehabilitation therapy. Most people with transverse myelitis experience at least partial recovery, which can take as long as several years. Intensive rehab once recovery begins is fully warranted.

T.F. Scott, MD et al, Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

Evidence-based guideline: Clinical evaluation and treatment of transverse myelitis

Neurology December 13, 2011 vol. 77 no. 24 2128-2134

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MRI in the Diagnosis and Followup of Multiple Sclerosis – pro

M Levin, MD — Mon, 02 Jul 2012 16:43:07 +0000

Magnetic Resonance Imaging (MRI) of the brain is useful in the diagnosis and treatment of multiple sclerosis (MS), because it is an inflammatory, demyelinating condition of the central nervous system (CNS) that MRI can visualize. Therefore, the activity of the disease can be quantified and tracked over time, with treatment. White matter tracts are affected, including those of the upper brain, lower brain, and spinal cord. MS lesions, known as plaques, may form in white matter in any location; thus, clinical symptoms may be diverse depending on where in the brain or spinal cord the disease is most active. MRI can identify the activity and explain the symptoms. MRI was widely used to in the diagnosis of multiple sclerosis (MS) and increasingly in follow-up. At the same time, it was not entirely clear how to use MRI. A consensus meeting was convened in 2008 to review and update the guidelines. The new guidelines incorporate new information and practice recommendations that will benefit patients and will be useful for
physicians and care providers. This consensus recommends a for a baseline evaluation for patients with a Clinically Isolated Syndrome (CIS) and suspected MS. A Brain MRI with gadolinium, a Spinal Cord MRI if there is persisting uncertainty about the diagnosis and/or the findings on Brain MRI are equivocal should be performed, as well as a Spinal Cord MRI if presenting symptoms or signs are at the level of the spinal cord.

Consortium of MS Centers MRI Protocol for the Diagnosis and Followup of MS 2009 REVISED GUIDELINES
http://mscare.org/cmsc/images/pdf/mriprotocol2009.pdf

Diffusion MR imaging in multiple sclerosis: technical aspects and challenges. AJNR 2007;28:411-420.

Stankiewicz JM, Glanz BI, Healy BC, Arora A, Neema M, Benedict RH, et al. Brain MRI Lesion Load at 1.5T and 3T versus Clinical Status in Multiple Sclerosis. J Neuroimaging. Nov 3 2009

Jordan JE, Wippold FJ II, Cornelius RS, Amin-Hanjani S, Brunberg JA, Davis PC, De La Paz RL, Dormont D, Germano I, Gray L, Mukherji SJ, Seidenwurm DJ, Sloan MA, Turski PA, Zimmerman RD, Zipfel GJ, Expert Panel on Neurologic Imaging. ACR Appropriateness Criteria® headache. [online publication]. Reston (VA): American College of Radiology (ACR); 2009. 8 p. [51 references]

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