John J. Wald

Chronic inflammatory demyelinating polyradiculoneuropathy in children: I. Presentation, electrodiagnostic studies, and initial clinical course, with comparison to adults

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is rare in children. We reviewed features of 15 children with idiopathic CIDP, and compared these to 69 adults with idiopathic CIDP. Children demonstrated many similarities to adults: (1) Antecedent events were uncommon. (2) There was a high frequency of weakness and reflex loss, a relatively high frequency of sensory loss, and a low frequency of pain and cranial neuropathies. (3) Cerebrospinal fluid protein levels were usually elevated. (4) On electrodiagnostic testing, not all nerve segments were abnormal, and not all children satisfied electrodiagnostic criteria for CIDP. Children differed from adults with CIDP in several ways: (1) The onset of symptoms was usually more precipitous. (2) Gait abnormalities were a more frequent presenting symptom. (3) Children always presented with significant neurological dysfunction, and not with the minor symptoms initially seen in some adults. The initial response of children with CIDP to immunomodulating therapy was excellent.

Chronic inflammatory demyelinating polyradiculoneuropathy in children: II. Long-term follow-up, with comparison to adults

We previously reviewed the presentation, initial clinical course, and electrodiagnostic features of children with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We now report the long‐term follow‐up of 12 children with idiopathic CIDP, and compare these to 62 adults with idiopathic CIDP. Children often had more rapidly fluctuating courses than adults. A relapsing course was significantly more common in children than in adults. The recovery of children from each episode of deterioration was usually excellent, and better, on average, than in adults. Ventilatory support was never required for children with slowly evolving illness; only 2 children with a precipitous onset clinically resembling Guillain‐Barré syndrome required ventilatory support. Prednisone, plasma exchange, and intravenous immunoglobulin (IVIg) usually were effective in children. Multiple courses of IVIg could be given with continued efficacy. Treatment often could be discontinued in children with relapsing courses. The prognosis for children was excellent. Adults demonstrated a good, but more variable, outcome.

Phenotypic analysis of autosomal dominant hereditary spastic paraplegia linked to chromosome 8q.

Objective: To describe clinical, electrophysiologic, neuroimaging, and muscle biopsy features in a hereditary spastic paraplegia (HSP) kindred linked to a new HSP locus on chromosome 8q. Background: HSP is a genetically diverse group of disorders characterized by insidiously progressive spastic weakness in the legs. We recently analyzed a Caucasian kindred with autosomal dominant HSP and identified tight linkage to a novel HSP locus on chromosome 8q23-24. Methods: Clinical analysis, nerve conduction studies, electromyography, somatosensory evoked potentials, MRI of brain and spinal cord, and muscle biopsy for mitochondrial analysis were performed in members of the first HSP kindred linked to chromosome 8q. Results: Fifteen individuals showed insidiously progressive spastic paraparesis beginning between ages 22 and 60 years (average, 37.2 years). Spinal cord MRI in 1 moderately affected subject showed significant atrophy of the thoracic spinal cord as determined by cross-sectional area measurements. Somatosensory evoked potential recording, electromyography, nerve conduction studies, and muscle biopsy, including histochemical and biochemical analysis of mitochondrial function, were normal. Conclusions: The phenotype in this family is that of typical, but severe, uncomplicated HSP. Other than apparently increased severity, there were no clinical features that distinguished this family from autosomal dominant HSP linked to loci on chromosomes 2p, 14q, and 15q. This clinical similarity between different genetic types of autosomal dominant HSP raises the possibility that genes responsible for these clinically indistinguishable disorders may participate in a common biochemical cascade. Normal results of muscle histochemical and biochemical analysis suggest that mitochondrial disturbance, a feature of chromosome 16-linked autosomal recessive HSP due to paraplegin gene mutations, is not a feature of chromosome 8q-linked autosomal dominant HSP and may not be a common factor of HSP in general.

Randomized trial of azathioprine or prednisone for initial immunosuppressive treatment of myasthenia gravis

Ten patients with myasthenia gravis were randomized to azathioprine or prednisone as the initial immunomodulating drug and followed for over one year. Of five patients randomized to azathioprine, two had idiosyncratic reactions and were immediately crossed over to prednisone. Two patients completed one year on azathioprine with little or no change in level of function and were crossed over to prednisone and showed greater improvement. The fifth patient on azathioprine had a satisfactory improvement and continued on it during the second year. All patients initially randomized to prednisone improved, but the degree varied among patients. The side effects of azathioprine were idiosyncratic reactions. The side effects of prednisone were manageable.

Granulomatous myositis, primary biliary cirrhosis, pancytopenia, and thymoma

Granulomatous myopathies are rare. Most cases are associated with sarcoidosis. We report a case of granulomatous myopathy associated with primary biliary cirrhosis, pancytopenia, and thymoma. The literature in regard to granulomatous myopathy and its pathogenesis is reviewed. Intermittent pulsed intravenous methylprednisolone may be useful as maintenance therapy for granulomatous myopathy and other neuromuscular syndromes for patients intolerant of oral corticosteroids.

Autosomal recessive primary generalized dystonia in two siblings from a consanguineous family

We describe the clinical features of a brother and sister with non–dopa‐responsive, childhood‐onset, generalized dystonia. The children were born to consanguineous parents, had no family history of neurologic disease, no evidence of structural or metabolic causes of dystonia, and negative testing for the GAG946 deletion mutation in the DYT1 gene. This report supports the existence of a generalized type of dystonia with autosomal recessive inheritance (DYT2).

Spastic paraplegia, ataxia, mental retardation (SPAR): A novel genetic disorder

ObjectiveTo describe a kindred with a dominantly inherited neurologic disorder manifested either as uncomplicated spastic paraplegia or ataxia, spastic paraplegia, and mental retardation. MethodsNeurologic examinations and molecular genetic analysis (exclusion of known SCA and HSP genes and loci; and trinucleotide repeat expansion detection [RED]) were performed in six affected and four unaffected subjects in this family. MRI, electromyography (EMG), and nerve conduction studies were performed in three affected subjects. ResultsThe phenotype of this dominantly inherited syndrome varied in succeeding generations. Pure spastic paraplegia was present in the earliest generation; subsequent generations had ataxia and mental retardation. MRI showed marked atrophy of the spinal cord in all patients and cerebellar atrophy in those with ataxia. Laboratory analysis showed that the disorder was not caused by mutations in genes that cause SCA-1, SCA-2, SCA-3, SCA-6, SCA-7, SCA-8, and SCA-12; not linked to other known loci for autosomal dominant ataxia (SCA-4, SCA-5, SCA-10, SCA-11, SCA-13, SCA-14, and SCA-16); and not linked to known loci for autosomal dominant hereditary spastic paraplegia (HSP) (SPG-3, SPG-4, SPG-6, SPG-8, SPG-9, SPG-10, SPG-12, and SPG-13) or autosomal recessive HSP SPG-7. Analysis of intergenerational differences in age at onset of symptoms suggests genetic anticipation. Using RED, the authors did not detect expanded CAG, CCT, TGG, or CGT repeats that segregate with the disease. ConclusionsThe authors describe an unusual, dominantly inherited neurologic disorder in which the phenotype (pure spastic paraplegia or spastic ataxia with variable mental retardation) differed in subsequent generations. The molecular explanation for apparent genetic anticipation does not appear to involve trinucleotide repeat expansion.

Juvenile myasthenia gravis: Treatment with immune globulin and thymectomy

Juvenile myasthenia gravis is rare, representing just 10% of all myasthenia gravis. Treatment of the juvenile form is similar to the adult form, although concerns of long-term side effects limit use of immunomodulators and thymectomy in children, especially the very young. We review the clinical course of three children with juvenile myasthenia gravis, as well as the current status of intravenous immunoglobulin and thymectomy as treatments for juvenile myasthenia gravis.

Botulinum toxin injection in the treatment of vocal fold paralysis associated with multiple sclerosis: A case report

Botulinum toxin has been demonstrated clinically to be an effective treatment for a variety of laryngeal problems, most notably spasmodic dysphonia. As in other movement disorders, the theory behind the injection of this substance in the larynx has been a weakening of the vocal fold musculature to relieve uncoordinated and spasmodic movement of the vocal folds, presumably rebalancing the forces within the intralaryngeal musculature. Recently, this concept was applied to help reposition the arytenoid cartilage in acute and longstanding anteromedial cricoarytenoid dislocations. This same concept may apply to the paralyzed vocal fold. In support of this idea, a number of investigators have shown that immobile, clinically paralyzed vocal folds may still have partial voluntary motor unit activity. This voluntary activation may not produce clinically evident movement but may be sufficient to produce tone within the fold. If the voluntary motor units in the abductor musculature of the paralyzed fold are weakened with botulinum toxin, the continued pull of the functioning adductor musculature may be sufficient to medialize the paralyzed fold. This idea has been supported by animal experiments, which have shown that botulinum toxin may affect the ability of the fold to rebalance itself. With this evidence in mind, a patient with fold immobility secondary to multiple sclerosis was treated in an attempt at laryngeal rebalancing, using botulinum toxin to medialize the fold. However, instead of simply having the fold return fixed to the midline, the patient regained normal laryngeal mobility and voice. While it is unclear whether the botulinum toxin alone was responsible, the coincidence of this occurrence certainly requires reporting. This paper is a report of the first successful treatment of vocal fold paralysis using botulinum toxin to treat vocal fold fixation in a patient with multiple sclerosis.

Neurologic evaluation of workers previously diagnosed with solvent-induced toxic encephalopathy.

We examined 52 railroad workers with long-term occupational solvent exposures (average 22 years duration) who had been previously diagnosed by others as having solvent-induced toxic encephalopathy. All described episodes of transient intoxication associated with occupational solvent exposure. Persistent symptoms developed, an average, 16 years after exposure onset and included impaired memory (38), altered mood (21), imbalance (18), and headache (17). Thirteen workers had mild mental status abnormalities, but none fulfilled conventional clinical criteria for encephalopathy or dementia. None had abnormal blink reflex (51) or abnormal electroencephalographic (39) studies. Eight of 47 magnetic resonance imaging studies showed evidence of scattered ischemic lesions among workers with known diabetes mellitus (2), elevated blood pressure (4), or peripheral vascular disease (2). One magnetic resonance imaging scan showed mild cortical atrophy. In stepwise multiple linear and logistic regression models, no statistically significant (P < 0.05) dose-response relationships were found between exposure duration and symptoms or signs that were suggestive of encephalopathy. However, the number of symptoms (P < 0.001) and the number of signs (P = 0.05) were associated with current use of central nervous system-active medications. Further, lower Mini-Mental Status Examination scores were associated with a history of alcohol abuse (P = 0.01) and lower educational level (P = 0.03). The number of chief symptoms involving memory, mood, balance, or headache differed significantly among workers in different geographic sites (F(3.48) = 2.94, P = 0.04), a finding that was not explained by job title or exposure duration. There also was a significant (P = 0.0001) inverse relationship between initial exposure year (r2 = 0.60) or total years of exposure through 1987 (r2 = 0.56) and interval to major neurologic symptom onset, suggesting that factors other than solvent exposure account in part for worker complaints. We found no objective neurologic evidence supportive of toxic encephalopathy or any other uniform syndrome among these individuals, and most complaints were explained by neuropsychological factors or conditions unrelated to occupational solvent exposure.