McLeod myopathy revisited: more neurogenic and less benign

Abstract

The X-linked McLeod neuroacanthocytosis syndrome (MLS) has originally been denoted as 'benign' McLeod myopathy. We assessed the clinical findings and the muscle pathology in the eponymous index patient, Hugh McLeod, and in nine additional MLS patients. Only one patient had manifested with neuromuscular symptoms. During a mean follow-up of 15 years, however, eight patients including the initial index patient showed elevated skeletal muscle creatine kinase levels ranging from 300 to 3000 U/L, and had developed muscle weakness and atrophy. Two patients had disabling leg weakness. Muscle histology was abnormal in all 10 patients. Clear but unspecific myopathic changes were found in only four patients. All patients, however, had neurogenic changes of variable degree. Post-mortem motor and sensory nerve examinations support the view that muscle atrophy and weakness are predominantly due to an axonal motor neuropathy rather than to a primary myopathy. Multisystem manifestations developed in eight patients at a mean age of 39 years. Three patients manifested with psychiatric features comprising schizophrenia-like psychosis and personality disorder, two presented with generalized seizures and one with chorea. During follow-up, seven patients developed chorea, six had psychiatric disorders, five had cognitive decline and three had generalized seizures. Five patients died because of MLS-related complications including sudden cardiac death, chronic heart failure and pneumonia between 55 and 69 years. In conclusion, our findings confirm that MLS is not a benign condition but rather a progressive multisystem disorder sharing many features with Huntington's disease.

Une cause inhabituelle d’hyperCKémie

“…Les complications ou manifestations neuromusculaires n'y sont pas rares et peuvent prendre plusieurs formes : neuropathie sensitivomotrice, ou plus souvent atteinte myopathique de sévérité variable allant d'une simple hyperCKémie, (avec, il faut le souligner, un risque non négligeable de rhabdomyolyse), jusqu'à des tableaux exceptionnellement déficitaires. Une cardiomyopathie a également été rapportée à plusieurs reprises dans la litté-rature, généralement après la cinquantaine [5,6,8]. McLeod mais ceci n'a jamais pu être formellement démontré [9].…”

Feeding dystonia: A classical presentation of neuroacanthocytosis

“…The patients have elevated creatinine kinase levels and axonal neuropathy. The neuromuscular involvement in choreoacanthocytosis includes myopathy and axonal sensorymotor neuropathy [5]. McLeod syndrome should be considered as a differential diagnosis of choreoacanthocytosis as neuromuscular involvement is more common in this subtype of neuroacanthocytosis [6].…”

Cardiac and neurologic involvement in McLeod syndrome

“…Recently, however, it has been shown that only 40% of the patients exhibit non-specific myopathic changes on muscle biopsy, whereas 100% exhibit neurogenic changes due to axonal neuropathy [2]. Which was the cause of CKelevation in the presented patients?…”

“…Only two of six patients (33%) developed weakness or wasting, despite a mean age of 45 years. In a recent study on 10 patients, however, 80% developed weakness and wasting within a mean observational period of 15 years [2]. How to explain this discrepancy?…”

“…Central nervous system manifestations in McLeod syndrome not only include chorea, psychiatric disorders, or cognitive impairment but also seizures [2]. How many of the included patients had developed epilepsy?…”