Corticospinal tract degeneration in the progressive muscular atrophy variant of ALS.

OBJECTIVE: Examining the unresolved relationship between the lower motor neuron disorder progressive muscular atrophy (PMA) and ALS is important in clinical practice because of emerging therapies. METHODS: Spinal and brainstem tissues donated from patients with ALS/motor neuron disorder (n = 81) were examined. Using retrospective case note review, the authors assigned patients into three categories: PMA (12), PMA progressing to ALS (6), and ALS ab initio (63). Conventional stains for long tract degeneration and immunocytochemistry for ubiquitin and the macrophage marker CD68 were examined. RESULTS: Rapid progression and typical ubiquitinated inclusions in lower motor neurons were present in 77 (95%) of the cases. Immunocytochemistry for CD68 was a more sensitive marker of long tract pathology in comparison with conventional stains. Half of the cases with PMA showed corticospinal tract degeneration by CD68. CONCLUSION: Patients with PMA frequently have undetected long tract pathology and most have ubiquitinated inclusions typical of ALS. A patient presenting with PMA with rapid clinical evolution likely has the pathology and pathophysiology of ALS whether or not upper motor neuron signs evolve.

McLeod neuroacanthocytosis: genotype and phenotype.

McLeod syndrome is caused by mutations of XK, an X-chromosomal gene of unknown function. Originally defined as a peculiar Kell blood group variant, the disease affects multiple organs, including the nervous system, but is certainly underdiagnosed. We analyzed the mutations and clinical findings of 22 affected men, aged 27 to 72 years. Fifteen different XK mutations were found, nine of which were novel, including the one of the eponymous case McLeod. Their common result is predicted absence or truncation of the XK protein. All patients showed elevated levels of muscle creatine phosphokinase, but clinical myopathy was less common. A peripheral neuropathy with areflexia was found in all but 2 patients. The central nervous system was affected in 15 patients, as obvious from the occurrence of seizures, cognitive impairment, psychopathology, and choreatic movements. Neuroimaging emphasized the particular involvement of the basal ganglia, which was also detected in 1 asymptomatic young patient. Most features develop with age, mainly after the fourth decade. The resemblance of McLeod syndrome with Huntington's disease and with autosomal recessive chorea-acanthocytosis suggests that the corresponding proteins--XK, huntingtin, and chorein--might belong to a common pathway, the dysfunction of which causes degeneration of the basal ganglia.