[Man aged 49 years suffering from progressive clinical picture with palatal tremor, segmental myoclonus, ataxia, parkinsonism, amyotrophy, pyramidal signs, supranuclear ophthalmoplegia and cognitive decline]. / Varón de 49 años con cuadro progresivo de temblor palatino, mioclono segmentario, ataxia, parkinsonismo, amiotrofia, piramidalismo, oftalmoplejía supranuclear y trastorno cognitivo.

In this clinicopathological conference we discuss the case of a patient aged 49 years, who developed progressive clinical picture characterized by palatal tremor (PT), segmental myoclonus, cerebellar ataxia, parkinsonism, amyotrophy, pyramidal signs, supranuclear ophthalmoplegia, parkinsonism and cognitive decline. He died 10 years after onset. There was no family history of ataxia. Initially a diagnosis of cerebral Whipple's disease was given, but prolonged treatment with ampicilin and cloramfenicol did not modify the clinical course. Magnetic resonance imaging study showed cerebellar and brainstem atrophy. Electrophysiological examination revealed neurogenic electromyographic pattern and abnormal somatosensory and brainstem evoked potentials. Starting from symptomatic PT, as the guide sign, a presumptive pathological diagnosis of sporadic olivopontocerebellar atrophy (OPCA) was established, probably of multiple system atrophy (MSA) type. Neuropathological study demonstrated OPCA with preferential involvement of cerebellum but without glial inclusions. This case illustrates the great clinicopathological complexity of OPCA and that not all forms of sporadic OPCA may be included within MSA.

Varón de 49 años con cuadro progresivo de temblor palatino, mioclono segmentario, ataxia, parkinsonismo, amiotrofia, piramidalismo, oftalmoplejía supranuclear y trastorno cognitivo / Man aged 49 years suffering from progressive clinical picture with palatal tremor, segmental myoclonus, ataxia, parkinsonism, amyotrophy, pyramidal signs, supranuclear ophthalmoplegia and cognitive decline

En esta sesión clinicopatológica se discute el caso de un paciente que a los 49 años desarrolló un cuadro clínico progresivo caracterizado por temblor palatino (TP), mioclono segmentario, ataxia, parkinsonismo, amiotrofia, piramidalismo, oftalmoplejía supranuclear y trastornos conductuales. El paciente falleció a los 10 años del inicio sintomático. No existían antecedentes familiares de ataxia. Inicialmente se sospechó que el síndrome se debía a una enfermedad de Whipple cerebral, lo que motivó un tratamiento prolongado con ampicilina y cloramfenicol que no modificó el curso clínico. El examen de resonancia magnética puso de manifiesto atrofia del cerebelo y tronco cerebral. Los estudios neurofisiológicos demostraron un electromiograma neurógeno y alteración de los potenciales evocados somatosensoriales y de tronco cerebral. Tomando como síntoma guía el TP sintomático, se establece una sospecha diagnóstica de atrofia olivopontocerebelosa (AOPC) esporádica, probablemente del tipo de la atrofia multisistémica (AMS). El estudio neuropatológico demostró una AOPC con afección preferente del cerebelo, pero sin inclusiones gliales. Este caso ilustra la complejidad clinicopatológica de la AOPC y que no todas las formas esporádicas de AOPC son equiparables con la AMS (AU)

Arginine-164-tryptophan substitution in connexin32 associated with X linked dominant Charcot-Marie-Tooth disease.

A Spanish family with X linked dominant Charcot-Marie-Tooth (CMTX1) neuropathy was screened for point mutations in the connexin32 gene (GJ beta 1). The patients showed a C-T transition at position 552 which predicts arginine to tryptophan substitution at amino acid 164 (R164K). This mutation destroys an AciI restriction site at position 552 and creates a PflMI restriction site.

Axonal form of Guillain-Barré syndrome: evidence for macrophage-associated demyelination.

We report on the clinical, electrophysiological, and pathological findings in a patient with pure motor and axonal Guillain-Barré syndrome, who died 29 days after onset. There was marked reduction of compound motor action potential amplitudes and denervation potentials in the tibialis anterior muscle. Motor and sensory conduction velocities of median nerve were normal. Peroneal nerve was inexcitable at the ankle but its latency from knee to tibialis anterior was normal. F waves were absent or delayed. The major burden of pathological changes fell on ventral spinal roots. Fundamental lesions included segmental demyelination, axonal degeneration, widespread endoneurial lipid-laden macrophage infiltrates, remyelination, and clusters of small regenerating fibers. These findings suggest that axonal damage in the axonal form of Guillain-Barré syndrome is secondary to demyelination.

Reversible Schwann cell hypertrophy in lead neuropathy.

Schwann cell hypertrophy is an early change observed in lead-induced neuropathy in the rat. In order to quantify this cell hypertrophy, a morphometric analysis of Schwann cell cytoplasmic and nuclear areas and their relationship to the cross-sectional area of the associated myelinated fibre was performed. The study was carried out on sural and peroneal nerves from three groups of adult rats. Group I was intoxicated with 4% lead acetate in the drinking water for 6 weeks; group II animals were treated as in group I and then restored to standard laboratory conditions for 30 days; and group III were controls. The results showed that: (a) after 6 weeks of lead exposure, cytoplasmic and nuclear areas were significantly greater in intoxicated, compared with control rats; (b) after 30 days recovery, Schwann cell cytoplasmic and nuclear areas did not differ from control rats.

Recovery of the early cellular changes induced by lead in rat peripheral nerves after withdrawal of the toxin.

A morphological and quantitative investigation was carried out in the peripheral nerves of adult rats, which were first exposed to 4% lead acetate in the drinking water and then restored to standard laboratory conditions. After six weeks of continuous lead exposure, the only cells involved were Schwann cells (SC) and endothelial cells (EC). As compared to age-matched controls, the most conspicuous changes observed by light and electron microscopy in these cells included the presence of nuclear inclusion bodies (NIB), cytoplasmic hypertrophy, mitochondrial abnormalities, an increased number of myelin-derived SC intracytoplasmic structures, and vesiculation of myelin sheaths. By counting the number of nuclear profiles containing NIB in semithin sections stained with basic fuchsin and methylene blue, we found that SC from predominantly cutaneous (sural) nerves were less vulnerable to lead than SC from mixed (peroneal) and muscular (tibial) nerves. With respect to EC, however, no significant differences were found among these three nerves. After termination of lead exposure, we observed a gradual decrease of most of the above cellular changes, which finally disappeared at day 30 post-intoxication. However, the number of myelin-related SC cytoplasmic bodies still remained above normal levels at the time of the termination of the experiment (60 days post-intoxication). The nature of the changes induced by lead in peripheral nerve cells as well as the rapid and nearly complete recovery suggest that they reflect a compensatory response to overcome the adverse effects of the lead on cell metabolism.

Laminated cytoplasmic bodies in Schwann cells and phagocytes: an ultrastructural and cytochemical study in the normal and lead-damaged peripheral nervous system of the rat.

We studied the distribution and cytochemical characteristics of laminated bodies (LBs) in the peripheral nervous system of normal and lead-intoxicated rats. In normal rats, LBs were exclusively present in myelin-forming Schwann cells (SCs). Nerves from lead-intoxicated animals showed extensive demyelination and remyelination. In these nerves we found an increase of LBs in the SC cytoplasm, and also within phagocytes involved in myelin removal, but not in remyelinating SCs. Cytochemical studies revealed that LBs were positive for acid phosphatase, thus demonstrating the lysosomal nature of such inclusions. Taken together, these data suggest that LBs are autophagolysosomes derived from myelin catabolism, which may be enhanced in the lead-induced demyelinating neuropathy of the rat. The possible mechanisms underlying this phenomenon and their pathological relevance are discussed.

Demyelination-induced plasticity in the axon membrane: an ultrastructural cytochemical study of lead neuropathy in the rat.

We examined the distribution of ferric ion-ferrocyanide stain (a marker for excitable regions of myelinated fibers) in the lead-induced demyelinating neuropathy of the rat. By electron microscopy, we found that paranodal degeneration resulted in spreading of the reaction product from nodal to internodal axolemma. During repair, nodal-like stained areas formed at the contact zones between preremyelinating Schwann cells. These data suggest that the location and extent of excitable axonal regions are influenced by axoglial relationships. Additionally, some fibers displayed staining at paranodal axolemma adjacent to demyelinated segments, suggesting it might be an alternative site for impulse generation in demyelinated fibers.

Cerebral arterial occlusion and intracranial venous thrombosis in a woman taking oral contraceptives.

Occlusion of the middle cerebral artery and thrombosis of the superior sagittal sinus are reported in a 30-year-old woman taking oral contraceptives (OC). The coexistence of arterial and venous cerebral pathology as a complication of OC use has only been previously reported in one case. The pathogenesis of this rare association is briefly discussed.