Bruce Day

Development of Neuropathy in Patients With Myeloma Treated With Thalidomide: Patterns of Occurrence and the Role of Electrophysiologic Monitoring

PURPOSE Peripheral neuropathy frequently limits the duration of treatment with thalidomide for patients with multiple myeloma. We assessed the time course of occurrence, possible predictive factors, and the utility of serial nerve electrophysiological studies (NES) for detecting onset of neuropathy. PATIENTS AND METHODS Seventy-five patients with relapsed/refractory myeloma were enrolled onto a multicenter trial of dose-escalating thalidomide with or without interferon. Patients underwent clinical assessment plus NES at baseline and every 3 months. Time to development of neuropathy according to clinical or NES criteria was compared. Patient and treatment-related factors were compared as predictors of neuropathy. RESULTS Thirty-nine percent had some NES abnormalities at baseline. Patients received thalidomide at a median dose-intensity of 373 mg/d. Thirty-one of 75 patients (41%) developed neuropathy during thalidomide treatment; 11 patients (15%) discontinued treatment with thalidomide due to neuropathy. The actuarial incidence of neuropathy increased from 38% at 6 months to 73% at 12 months, with 81% of responding patients developing this complication. Serial NES did not reliably predict the imminent development of clinical neuropathy requiring thalidomide cessation, nor were patient age, sex, or prior therapy predictive. Patients who developed neuropathy had a longer duration of thalidomide exposure (median, 268 v 89 days; P = .0001). Cumulative dose or dose-intensity received was not predictive. CONCLUSION The majority of patients will develop peripheral neuropathy given sufficient length of treatment with thalidomide. To minimize the risk of neurotoxicity, therapy should be limited to less than 6 months. Electrophysiologic monitoring provides no clear benefit versus careful clinical evaluation for the development of clinically significant neuropathy.

Psychogenic propriospinal myoclonus

We report a case of probable psychogenic propriospinal myoclonus (PSM) in a patient who developed a sudden onset of disabling axial flexor myoclonus following a cosmetic surgical procedure. The electrophysiological findings were consistent with previous reports of PSM. Spontaneous remissions and disappearance of the jerks, sustained for 2 years, following removal of superficial surgical screws support the diagnosis of a psychogenic movement disorder.

Speech-activated myoclonus: an uncommon form of action myoclonus.

We describe an unusual form of facial myoclonus activated by speech in 3 patients with different underlying neurological diseases and present the electrophysiological investigations and results of structural and functional imaging. In 1 of 2 patients in whom jerk‐locked electroencephalogram (EEG) back‐averaging was done, a cortical potential clearly preceded the facial jerks. In the second patient, a cortical potential preceding the jerk was not certain. In the third patient, the resting EEG contained outbursts of symmetric, slower frequencies of indeterminate significance. An epileptiform disorder was suspected in this patient.

Rippling muscle disease

A case of rippling muscle disease is presented and features of this rare condition, and its association with caveolin-3 are discussed.

Multifocal motor neuropathy and muscle hypertrophy

Multifocal motor neuropathy is frequently an asymmetrical neuropathy predominantly affecting the upper limbs. Patients present with weakness, fasciculations and distal muscle wasting. Hypertrophy of muscles is very infrequently reported. We present two cases of multifocal motor neuropathy with upper limb muscle hypertrophy and discuss possible pathophysiological mechanisms. Botulinum toxin may be useful to alleviate cramp.

077 Recurrent guillain-barre syndrome

Introduction Recurrent Guillain-Barre syndrome (GBS) is very rare. It occurs in 2% to 5% of GBS patients. It is unclear as to why some patients have a recurrence and whether this occurs more frequently in a distinct group of patients. We report a case of a 75 year old man who had five discreet attacks of GBS in 30 years. He had an excellent response to intravenous immunoglobulin (IVIG) and achieved full clinical recovery after each attack. Case A 75 year old man presented to the hospital with progressive ascending pattern of numbness and weakness in upper and lower limbs. This was in the setting of 10 days history of upper respiratory tract infective (URTI) symptoms. Neurological examination revealed distal sensory loss and distal weakness in upper and lower limbs. Deep tendon reflexes were absent. Nerve conduction studies showed features in keeping with GBS. He was treated with 5 days of intravenous immunoglobulin (IVIG) with significant improvement. Interestingly, this was on the background of having had 4 previous attacks of GBS in 1986 (preceded by acute gout), 1997 (preceded by the flu), 2010 (preceded by small bowel obstruction) and 2016 (preceded by viral gastroenteritis). He responded to IVIG each time and returned to his premorbid level function promptly after each attack. Conclusion Recurrent GBS is rare. It is important for clinician to be able to distinguish between recurrent GBS, treatment related fluctuations (GBS-TRF) and chronic inflammatory demyelinating polyneuropathy as the treatment and outcomes are different for each of these conditions. References . Kuitwaard K, Van Koningsveld R, Ruts L, Jacobs B, Van Doorn P. Recurrent Guillain Barre Syndrome. J Neurol Neurosurg Psychiatry2009;80:56–59. . Pyun SY, Jeong JH, Bae JS. Recurrent Guillain-Barré syndrome presenting stereotypic manifestations, positive antiganglioside antibodies, and rapid recovery. Clin Neurol Neurosurg2015Dec;139:230–3. . Mossberg N, Nordin M, Movitz C, Nilsson S, Hellstrand K, Bergström T, Andersson B, Andersen O. The recurrent Guillain-Barré syndrome: A long-term population-based study. Acta Neurol Scand2012Sep;126(3):154–61.

029 Multiple-acyl-coa dehydrogenase deficiency (MADD): a rare but treatable genetic metabolic myopathy

Introduction Multiple-acyl-CoA dehydrogenase deficiency or MADD is a rare autosomal recessive disorder caused by deficiency of electron transfer flavoprotein. Late onset form of MADD typically present with slowly progressive proximal weakness, myalgia, lethargy, vomiting, hypoglycaemia and metabolic acidosis. This condition is highly variable in age and symptoms at onset. The mean delay between onset of symptoms and diagnosis was 3.9 years. Confirmation of the diagnosis requires relatively complicated tests including muscle biopsy, Acylcarnitine profiling, urinary organic acid analysis and molecular gene testing. MADD responds dramatically to riboflavin supplementation and dietary treatment i.e. high carbohydrate, low fat and low protein diet. We report of a case of Multiple-Acyl-CoA Dehydrogenase Deficiency (MADD) and a review of the literature. Case A 22 year old female presented with 3 year history of slowly progressive muscle weakness, fatigue and dyspnea on minimal exertion. Clinical examination revealed profound neck extension weakness (‘dropped head syndrome’), proximal muscle weakness (winged scapula and positive Gower’s sign), mild dysphagia and dysarthria. There was no obvious facial weakness, ptosis or ophthalmoplegia. Muscle biopsy showed prominent lipid and generalised hypotrophy of type I fibres. The diagnosis of MADD was suspected on the basis of clinical presentation. The patient was commenced on riboflavin, carnitine supplementation and low protein, low fat diet. Her symptoms improved significantly over 2 months (improvement in muscle strength and respiratory function, FVC improved from 42% to 89%). Acylcarnitine and amino acid screen results came back later showing elevated levels of C6, C8, C10 and C12 in keeping with the diagnosis of MADD. Conclusion Multiple-acyl-CoA dehydrogenase deficiency is a rare genetic metabolic myopathy. It is under-recognised and diagnosis of the adult onset form is often challenging. The majority of patients respond well to riboflavin and dietary modifications with excellent clinical outcome. References . Sharp LJ, Haller RG. Metabolic and mitochondrial myopathies. Neurol Clin2014Aug;32:777–99. . Grunert SC. Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme: A dehydrogenase deficiency. Orphanet J Rare Dis2014Jul 22;9:117. . Angelini C. Spectrum of metabolic myopathies. Biochem Biophys Acta2015Apr;1852(4):615–21. . Yee WC. Two eminently treatable genetic metabolic myopathies. Neurol India2008Jul–Sep;56(3):333–8.

Painful numb hands

Carpal tunnel syndrome, resulting from median nerve compression at the wrist, is a common and often disabling mononeuropathy. Risk factors include female sex, family history, repetitive hand use, obesity, pregnancy and a variety of medical comorbidities including diabetes mellitus, rheumatoid arthritis, and other connective tissue diseases. In many cases, an accurate diagnosis can be reached on the basis of clinical history and supportive examination findings alone. Neurophysiological investigations are essential for confirming the diagnosis, assessing severity and excluding more generalised neuropathies, as well as providing a baseline preoperative index of median nerve function. Wrist splinting and local corticosteroid injection are effective treatments in the short term, but long‐term data are lacking. Surgical (endoscopic or open) carpal tunnel release is effective and nearly always required to enable a return to work for patients with occupationally induced carpal tunnel syndrome.

A Unique Case of Cortical Myoclonus Sensitive to Visual Stimuli in the Peripersonal Space

Multimodal representation of peripersonal or near space has been demonstrated in the brain of the nonhuman primate through invasive electrophysiological experiments. Representation of peripersonal space in the human brain has been inferred from extinction experiments and functional imaging studies. We present a unique case of lower limb myoclonus in a patient with common variable immunodeficiency which is sensitive to visual stimuli in the peripersonal space and light touch. This case provides further evidence for near space representation in the human brain. We hypothesize that somatopically organized multimodal areas exist in the human brain which code for peripersonal space.