Barend P. Lotz

Merosin‐negative congenital muscular dystrophy associated with extensive brain abnormalities

Congenital muscular dystrophies (CMDs) are autosomal recessive, heterogeneous disorders. The most frequent form in the Caucasian population is classic (occidental) CMD, characterized by exclusive muscle involvement, although abnormal brain white matter signals are occasionally observed on MRI. Recently, deficiency of merosin, the laminin isoform in skeletal muscle, has been identified in classic CMD patients. In skeletal muscle, merosin is a native ligand for dystroglycan linking the extracellular matrix and dystrophin. Thus, merosin deficiency could disrupt the attachment of muscle cell to the extracellular matrix and lead to muscle cell necrosis. Since merosin is also expressed in the nervous system and has biologic activities on neurite outgrowth and Schwann cell migration, deficiency of merosin could affect the development of the nervous system. We report here two patients with merosin-negative CMD presenting extensive brain abnormalities characterized by cortical anomaly, polymicrogyria, and abnormal white matter signals.

INFANTILE BOTULISM : PITFALLS IN ELECTRODIAGNOSIS

Botulism in infants, unless recognized early, is associated with high mortality and morbidity. The diagnosis is suspected when infants present with sudden onset of weakness, respiratory failure, and constipation and is confirmed by demonstration of botulinum toxin in stool several weeks later. Electrodiagnosis allows quick and reliable confirmation of botulism. Low-amplitude compound muscle action potentials, tetanic or post-tetanic facilitation, and the absence of post-tetanic exhaustion support the diagnosis. Two infants with confirmed botulism did not exhibit the characteristic electrodiagnostic features, demonstrating the pitfalls in electrodiagnosis of infantile botulism. (J Child Neurol 1999;14:156-158).

The rigid spine syndrome : a vacuolar variant

The rigid spine syndrome encompasses a number of disorders. We report 7 males and 2 females with this phenotype and a single, not previously reported, nosology. The salient muscle histological features were autophagic vacuoles, vacuoles containing capillaries, muscle spindle swelling, and type l fiber predominance. Disease onset was before age 6 years in all patients. Inheritance was probably autosomal recessive as siblings were affected in two families. Pulmonary function tests showed severely restricted ventilation, 3 patients required nocturnal ventilatory assistance, 2 patients had cor pulmonale, and mitral valve abnormalities were common. Serum CK levels were moderately elevated. EMG studies showed evidence of an active, chronic myopathy. The mean motor unit potential duration was statistically significantly shorter compared to controls in the triceps and anterior tibial muscles. Single fiber EMG “jitter” and evoked potential studies were normal.

Myopathic dropped head syndrome: an expanding clinicopathological spectrum.

Liao JP, Waclawik AJ, Lotz BP, Salamat SM, Beinlich BR, Brooks BR: Myopathic dropped head syndrome: an expanding clinicopathological spectrum. Am J Phys Med Rehabil 2007;86:970–976. Objective:A number of neuromuscular conditions may lead to a dropped head syndrome (DHS), with some patients developing a late onset noninflammatory myopathy affecting only, or predominantly, neck extensor muscles (NEM). The cause, pathogenesis, and nosological classification of this condition are unclear. To further investigate this condition, the authors evaluated the clinical, electrodiagnostic and pathologic findings in seven patients with a myopathic DHS. Design:Analysis of clinical data, electrodiagnostic studies, and muscle biopsies of seven patients, including one set of identical twins, who developed a very late onset myopathy with severe NEM weakness. Results:Age of onset was 61–79 yrs, with the pair of identical twins developing NEM weakness within 1 yr of each other (ages 63 and 64, respectively). Seven patients developed weakness (six slight weakness and one more severe) in muscles other than NEM. The group was characterized by the electromyography (EMG) showing a “myopathic” pattern in cervical paraspinal muscles (7/7), muscle biopsies with nonspecific myopathic changes on histologic stains (7/7), marked abnormalities in NADH dehydrogenase–reacted sections (6/7), desmin-positive sarcoplasmic deposits (1/7), low carnitine levels by biochemical assays (2/7), and mitochondrial changes (3/7). Conclusions:Myopathic DHS encompasses a wide spectrum of conditions that strongly affect NEM; however, as documented in the monozygotic twins, some patients may suffer from a distinct, genetically determined form of late-onset restricted myopathy leading clinically to DHS.

Dropped head syndrome.

To the Editor: Katz et al. [1] should be complimented for a very interesting presentation of a neuromuscular syndrome that has been increasingly recognized in neuromuscular clinics. We make the following comments. First, from our experience with several patients with a myopathic dropped head syndrome (DHS) who presented with similar clinical and pathologic findings as those noted by Katz et al., there is frequently, in addition to neck extensor weakness, mild weakness of other muscles, especially in the shoulder girdle region. However, because the neck extensor weakness is predominant and so severe, this mild degree of weakness in other muscle groups is frequently difficult to appreciate and may only be demonstrated on quantitative isometric muscle strength …

Muscle pathology and clinical features of the sarcolemmopathies

We report the clinical features and the muscle pathology in 2 patients with congenital muscular dystrophy (CMD) secondary to merosin deficiency and in 2 patients with sarcoglycan (adhalin) deficiency. Electron microscopic examination revealed sarcolemmal defects in non-necrotic muscle fibers in all cases. These pathological findings are indistinguishable from those of Duchenne/Becker muscular dystrophy. We suggest that the similarities in histological findings reflect a common pathogenetic mechanism, i.e., a structural weakening of the sarcolemma with an increased susceptibility to rupture under mechanical stress. We propose the term sarcolemmopathy as an all-encompassing rubric for these disorders.

CD8 and CD4 T cell-mediated polymyositis complicating the HTLV-1 associated myelopathy. Quantitative evaluation of corticosteroid treatment

Introduction – Inflammatory myopathy is a treatable cause of worsening in the spectrum of neurological conditions that may develop during the course of HTLV‐1 infection. Material and methods — To investigate the cause of subacute worsening in the strength of a 46‐y‐old black male with HTLV‐1 associated myelopathy we performed electrodiagnostic examination and a muscle biopsy which was studied with histochemistry, immunocytochemistry and electron microscopy. Serial measurements of isometric muscle strength were performed during the course of corticosteroid treatment. Results — The muscle biopsy showed evidence of denervation atrophy and prominent inflammatory changes with autoaggressive features. Lymphocyte typing showed a predominance of CD8+ T cells. The patient had sustained, marked improvement in strength, especially of the upper extremities, with oral, high single‐dose, alternate‐day prednisone therapy. Conclusion — A muscle biopsy should be considered in all patients with HTLV‐1 associated weakness, especially when electromyography indicates possible coexisting primary muscle involvement and/or serum creatine kinase levels are elevated. HTLV‐1‐associated polymyositis can be successfully treated with corticosteroids.

Congenital myopathy with ringlike distribution of myonuclei and mitochondria and accumulation of nemaline rods. A variant of centronuclear myopathy

Histopathologic and ultrastructural findings in a muscle biopsy performed on an 11-year old boy with congenital hypotonia, weakness, respiratory insufficiency requiring chronic ventilatory support, and a probable X-linked inheritance are presented. The muscle biopsy disclosed a peculiar, ringlike arrangement of mitochondria and myonuclei in most muscle fibers. Accumulations of nemaline rods were present in approximately 10-15% of fibers. We believe that our patient represents a variant of myotubular/centronuclear myopathy. The histochemical findings suggest disturbance in developmental migration of nuclei and mitochondria probably due to impaired function of the cytoskeleton.

Subclinical sensory involvement in monomelic amyotrophy.

An 18-year-old woman presented with weakness and atrophy in her hand without associated sensory symptoms, preceding events, or structural abnormalities on neuroimaging. No sensory deficits were detected on neurologic examination. Electrophysiological studies showed not only the expected motor findings for monomelic amyotrophy (MA) in the affected limb, but also markedly reduced sensory nerve action potentials when compared with the unaffected side. These findings suggest that subclinical sensory involvement can exist in patients with otherwise classic presentations of MA.