Sharon P. Nations

Multifocal acquired demyelinating sensory and motor neuropathy: The Lewis–Sumner syndrome

We report 11 patients with multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, defined clinically by a multifocal pattern of motor and sensory loss, with nerve conduction studies showing conduction block and other features of demyelination. The clinical, laboratory, and histological features of these patients were contrasted with those of 16 patients with multifocal motor neuropathy (MMN). Eighty‐two percent of MADSAM neuropathy patients had elevated protein concentrations in the cerebrospinal fluid, compared with 9% of the MMN patients (P < 0.001). No MADSAM neuropathy patient had elevated anti‐GM1 antibody titers, compared with 56% of MMN patients (P < 0.01). In contrast to the subtle abnormalities described for MMN, MADSAM neuropathy patients had prominent demyelination on sensory nerve biopsies. Response to intravenous immunoglobulin treatment was similar in both groups (P = 1.0). Multifocal motor neuropathy patients typically do not respond to prednisone, but 3 of 6 MADSAM neuropathy patients improved with prednisone. MADSAM neuropathy more closely resembles chronic inflammatory demyelinating polyneuropathy and probably represents an asymmetrical variant. Given their different clinical patterns and responses to treatment, it is important to distinguish between MADSAM neuropathy and MMN.

Myasthenia gravis activities of daily living profile

Article abstract The authors have developed an MG activities of daily living (ADL) profile (MG-ADL)—a simple eight-question survey of MG symptoms. In 254 consecutive encounters with established MG patients, the authors compared scores from the MG-ADL to the quantitative MG score (QMG)—a standardized, reliable scale used in clinical trials. The mean MG-ADL score was 4.89 ± 3.63. The mean QMG score was 10.80 ± 5.70. Pearson’s correlation coefficient was 0.583 (p < 0.001). The MG-ADL is an easy-to-administer survey of MG that correlates well with the QMG and can serve as a secondary efficacy measurement in clinical trials.

Denture cream An unusual source of excess zinc, leading to hypocupremia and neurologic disease

Background: Chronic, excess zinc intake can result in copper deficiency and profound neurologic disease. However, when hyperzincemia is identified, the source often remains elusive. We identified four patients, one previously reported, with various neurologic abnormalities in the setting of hypocupremia and hyperzincemia. Each of these patients wore dentures and used very large amounts of denture cream chronically. Objective: To determine zinc concentration in the denture creams used by the patients as a possible source of excess zinc ingestion. Methods: Detailed clinical and laboratory data for each patient were compiled. Tubes of denture adhesives were analyzed for zinc content using dynamic reaction cell-inductively coupled plasma-mass spectrometry. Patients received copper supplementation. Copper and zinc levels were obtained post-treatment at varying intervals. Results: Zinc concentrations ranging from about 17,000 to 34,000 μg/g were identified in Fixodent and Poli-Grip denture creams. Serum zinc levels improved in three patients following cessation of denture cream use. Copper supplementation resulted in mild neurologic improvement in two patients who stopped using denture cream. No alternative source of excess zinc ingestion or explanation for hypocupremia was identified. Conclusion: Denture cream contains zinc, and chronic excessive use may result in hypocupremia and serious neurologic disease.

Brachial amyotrophic diplegia: A slowly progressive motor neuron disorder

Objective: To describe a sporadic motor neuron disorder that remains largely restricted to the upper limbs over time. Background: Progressive amyotrophy that is isolated to the upper limbs in an adult often suggests ALS. The fact that weakness can remain largely confined to the arms for long periods of time in individuals presenting with this phenotype has not been emphasized. Methods: We reviewed the records of patients who had a neurogenic “man-in-the-barrel” phenotype documented by examination at least 18 months after onset. These patients had severe bilateral upper-extremity neurogenic atrophy that spared lower-extremity, respiratory, and bulbar musculature. Results: Nine of 10 patients meeting these criteria had a purely lower motor neuron disorder. During follow-up periods ranging from 3 to 11 years from onset, only three patients developed lower-extremity weakness, and none developed respiratory or bulbar dysfunction or lost the ability to ambulate. Conclusion: Patients presenting with severe weakness that is fully isolated to the upper limbs, without pyramidal signs, may have a relatively stable variant of motor neuron disease.

CLINICAL FINDINGS IN MUSK-ANTIBODY POSITIVE MYASTHENIA GRAVIS: A U.S. EXPERIENCE

We performed a retrospective chart review on 53 muscle‐specific kinase antibody (MuSK‐Ab)‐positive myasthenia gravis (MG) patients at nine university‐based centers in the U.S. Of these, 66% were Caucasian, 85% were women, and age of onset was 9–79 years. Twenty‐seven patients were nonresponsive to anticholinesterase therapy. Myasthenia Gravis Foundation of America improvement status was achieved in 53% patients on corticosteroids, 51% with plasma exchange, and in 20% on intravenous immunoglobulin (IVIG). Thymectomy was beneficial in 7/18 patients at 3 years. Long‐term (≥3 years) outcome was very favorable in 58% of patients who achieved remission and/or minimal manifestation status. Overall, 73% improved. There was one MG‐related death. This survey reinforces several cardinal features of MuSK‐Ab‐positive MG, including prominent bulbar involvement and anticholinesterase nonresponsiveness. Facial or tongue atrophy was rare. Most patients respond favorably to immunotherapy. The best clinical response was to corticosteroids and plasma exchange, and the poorest response was to IVIG. Long‐term outcome is favorable in about 60% of cases. Muscle Nerve, 2009

Randomized, controlled trial of intravenous immunoglobulin in myasthenia gravis.

We initiated a randomized, double‐blinded, placebo‐controlled trial of intravenous immunoglobulin (IVIG) treatment in myasthenia gravis (MG). Patients received IVIG 2 gm/kg at induction and 1 gm/kg after 3 weeks vs. 5% albumin placebo. The primary efficacy measurement was the change in the quantitative MG Score (QMG) at day 42. Fifteen patients were enrolled (6 to IVIG; 9 to placebo) before the study was terminated because of insufficient IVIG inventories. At day 42, there was no significant difference in primary or secondary outcome measurements between the two groups. In a subsequent 6‐week open‐label study of IVIG, positive trends were observed.

Open-label extension study following the Late-Onset Treatment Study (LOTS) of alglucosidase alfa

OBJECTIVE Late-onset Pompe disease is a progressive, debilitating, and often fatal neuromuscular disorder resulting from the deficiency of a lysosomal enzyme, acid α-glucosidase. This extension study was conducted to determine the durability of the efficacy and safety of alglucosidase alfa observed over a period of 78 weeks in the Late-Onset Treatment Study (LOTS). METHODS Patients who completed the LOTS study were eligible for this open-label extension study and received alglucosidase alfa 20mg/kg biweekly for an additional 26 weeks. The primary efficacy assessments were the distance walked during a 6-minute walk test and the percentage of predicted forced vital capacity in the upright position. Data are reported as change from patients original LOTS baseline for each measure. RESULTS The benefit of alglucosidase alfa treatment observed in LOTS at Week 78 was, in general, maintained at Week 104. The mean increase in distance walked measured 28.2 ± 66.5m from LOTS baseline to Week 78 and 21.3 ± 78.0m from LOTS baseline to Week 104. The mean change from baseline in percentage of predicted forced vital capacity was 1.3% ± 5.7% from LOTS baseline to Week 78 and 0.8% ± 6.7% from LOTS baseline to Week 104. Treatment-related adverse events were mainly infusion-associated reactions observed in 35% of patients. No deaths or anaphylactic reactions were observed during the extension study. CONCLUSIONS The LOTS Extension study showed that patients treated with alglucosidase alfa for up to 104 weeks maintained the improved walking distance and stabilization in pulmonary function observed in the first 78 weeks of alglucosidase alfa therapy.

Repetitive nerve stimulation of facial muscles in musk antibody–positive myasthenia gravis

To better define electrophysiological abnormalities in myasthenia gravis (MG) patients with muscle‐specific tyrosine kinase (MuSK) antibodies (Ab), we compared electrophysiological features of 14 MuSK Ab–positive, 73 acetylcholine receptor antibody (AChR Ab)–positive, and 22 MuSK and AChR Ab–negative (seronegative) patients with generalized disease. Repetitive nerve stimulation (RNS) abnormalities were observed in 86% of MuSK Ab–positive and 82% of AChR Ab–positive patients but in only 55% of seronegative patients. RNS decrements in the orbicularis oculi were more common and severe in the MuSK Ab–positive patients than the other two groups. Single‐fiber electromyography (SFEMG) of the extensor digitorum communis was abnormal in 90% of MuSK Ab–positive patients. The high frequency of RNS abnormalities in facial muscles in the MuSK Ab–positive population reflects the propensity for facial muscle involvement in this form of MG and emphasizes the importance of including facial muscles in RNS protocols when evaluating these patients. Muscle Nerve, 2006

Distal myasthenia gravis

Article abstract Myasthenia gravis (MG) characteristically involves ocular, bulbar, and proximal extremity muscles. Distal extremity muscles are typically spared or less prominently involved. The authors performed a retrospective chart review of MG patients treated at two university-based neuromuscular clinics. From a total population of 236, nine patients (3%) had distal extremity weakness exceeding proximal weakness by at least one Medical Research Council grade during their illness. Hand muscles, particularly finger extensors, were involved more frequently than were distal leg and foot muscles.

Reversible nitrous oxide-induced myeloneuropathy with pernicious anemia: Case report and literature review

A previously healthy 27‐year‐old woman developed a subacute myeloneuropathy after receiving nitrous oxide anesthesia for dental procedures. Neurologic evaluation revealed that she was vitamin B12 deficient due to underlying pernicious anemia. Discontinuation of nitrous oxide and supplementation with vitamin B12 resulted in dramatic clinical improvement, with near‐complete normalization of her neurologic examination. This case and published reports reviewed here emphasize that favorable outcomes are possible following prompt recognition and treatment of vitamin B12 deficiency. Muscle Nerve, 2007