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Background: Approximately half of Japanese sporadic Creutzfeldt-Jakob disease (sCJD) cases show panencephalopathic-type (PE-type) pathology, which is a rare subtype in North Americans and Europeans. Until now, the differences in the clinical course between subacute spongiform encephalopathy (SSE) cases and PE-type cases have been unclear., Methods: To investigate the clinical course of both subtypes, clinical findings from 42 Japanese MM1-type sCJD cases (20 SSE cases and 22 PE-type cases) were retrospectively evaluated by statistical analysis., Results: No significant differences could be found regarding age at disease onset, the period between disease onset and first observation of myoclonus, the period between disease onset and the first observation of periodic sharp-wave complexes on electroencephalogram, or the period between disease onset and progression to the akinetic mutism state - whereas total disease duration and the period between the akinetic mutism state and death were significantly longer in PE-type cases. The prolonged disease duration was induced by the extended survival period in the akinetic mutism state. There was a statistically significant difference between the two series regarding performance of tube-feeding, but no statistically significant difference regarding performance of tracheotomy or gastrostomy. None of the cases received mechanical ventilation., Conclusion: We speculate that the most crucial factor of the prolonged survival period of Japanese sCJD cases, particularly in the PE-type, is that the introduction of tube-feeding in the akinetic mutism state leads to the stabilization of the patient's general condition., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We present the case of an 81-year-old female with severe rigidity, stiffness and superimposed muscle spasms that represents the oldest reported patient with progressive encephalomyelitis with rigidity and myoclonus. Two associated autoimmune disorders (diabetes mellitus and Hashimoto's thyoiditis) were recently diagnosed. A paraneoplastic origin was excluded. The spectrum of differential diagnoses including classic Stiff-Person syndrome and paraneoplastic Stiff-Person syndrome is discussed.

A new model of cerebellar learning explains how the cerebellum can generate arbitrary output waveforms to adjust output timing in the classical delay conditioning. This model can also reproduce the low frequency ocular oscillations seen in oculopalatal tremor (OPT). A novel circuit in the cerebellum uses both interneurons (INs) and Purkinje cells (PC) to control timing. Brain lesions that cause OPT give rise to hypertrophy of the inferior olive (IO) and an increase in conductance through gap junctions among IO neurons. When our model is changed in this way, the heavily coupled IO becomes an oscillator and generates synchronous spike trains at 1-2 Hz. These synchronized spikes do not produce the large amplitude, aperiodic waveforms of OPT. However, the synchronized IO signal goes to the cerebellar cortex (flocculus) directly, on climbing fibres, and indirectly, on mossy fibres from the vestibular nuclei. This creates a pathological association between the IO pulse trains on mossy and climbing fibres in PC. Variable pendular ocular oscillations emerged from the cerebellum model after learning this association. Since electrotonic coupling of IO cells depends on connexin proteins, drugs that block gap junctions, such as anti-malarial agents, might provide a novel therapy for OPT.

We report a new family with palatal myoclonus, pyramidal tract signs, cerebellar signs, marked atrophy of the medulla oblongata and spinal cord, and autosomal dominant inheritance. These findings were almost identical with those in patients previously reported to have histopathologically confirmed adult-onset Alexander disease. Recently, heterozygous point mutations in the coding region of glial fibrillary acidic protein (GFAP) in patients with an infantile form of Alexander disease have been reported. We found a new heterozygous amino acid substitution, Val87Gly in exon 1 of GFAP, in the affected individuals in this family but not in 100 spinocerebellar ataxia (SCA) patients and 100 controls. Therefore, this family might have new clinical entities related to adult-onset Alexander disease and GFAP mutation.

Our aim was to localize the generator site of parasagittal epileptiform discharges in a patient with epilepsia partialis continua (EPC) in the right leg. We examined a 32-year-old woman with EPC whose conventional EEG did not show any epileptic discharge. We performed the jerk-locked back averaging (JLA) of EEG and magnetoencephalography (MEG) to localize the dipole source of sharp transients. The myoclonic discharges in the right soleus muscle were used as a trigger pulse. JLA revealed consistent EEG and MEG sharp transients that coincided consistently and constantly preceded the myoclonic jerks. JLA of EEG demonstrated sharp waves paradoxically distributed over the vertex and right hemisphere. However, the estimated dipoles of MEG were localized in a restricted area in the primary leg motor area in the left hemisphere, which was closely located in the abnormal lesion on the brain MRI. JLA of MEG is considered to be a useful non-invasive method for localizing the epileptogenic area in EPC even when paradoxical lateralization of electroencephalographic discharges was noted.

In an attempt to associate the clinical neurological syndromes with the neuropathological features of canine distemper (CD), 19 spontaneous cases with neurological involvement were examined, before and after euthanasia. Seventeen dogs were less than one year of age and all except two (89.4%) were unvaccinated against CD. Various extraneural signs associated with CD encephalomyelitis (CDE) were seen in 15 dogs. Generalized or localized myoclonus was the most common sign observed (13/19). Seventeen of the dogs presented with signs suggestive of one neuroanatomical location of lesions. Of these animals, seven had signs of cerebral, two of cerebellar, four of cervical, one of cervicothoracic, two of thoracolumbar and two of lumbosacral syndrome. The diagnosis of CD was confirmed immunohistochemically (detection of CD viral antigen), serologically (neutralizing serum antibody titre > or = 16) and histopathologically (CDV inclusion bodies, type of central nervous system lesions). An association of the neuroanatomical lesion location and the histopathological findings was noted in 14 out of 17 dogs (82.3%). Myoclonus could be attributed to lower motor neuron damage in eight out of 13 dogs (61.5%).

A 52-year-old, right-handed female presented with visuospatial dysfunction including left hemineglect, incomplete Balint's syndrome, and environmental agnosia, together with left-sided motor symptoms such as unskillful movement, dystonic postures, and myoclonus in the left hand, without significant dementia. Symptoms progressed to akinetic mutism prior to her death 10 years after onset of illness. Imaging studies such as MRI, SPECT, and PET studies showed severe, predominantly right-sided involvement of parietal and parieto-occipital areas. The motor signs might originate from the right parietal lesions such as area five or somatosensory area. Neuropathologic studies including immunocytochemistry showed tau-positive neurofibrillary tangles and abundant neuritic plaques with amyloid deposits, confirming the diagnosis of Alzheimer's disease. An analysis of serum apolipoprotein E revealed epsilon3/epsilon3 homozygosity. This case represents a variant of Alzheimer's disease conspicuous for progressive motor signs and visuospatial dysfunction with a striking laterality, reflecting asymmetric parietal involvement. Alzheimer's disease with asymmetric parietal atrophy is difficult to be clinically distinguished from corticobasal degeneration characterized by progressive unilateral motor signs and focal cortical signs.

Purpose: The one-and-a-half syndrome is an eye movement disorder characterized by a unilateral gaze palsy and an ipsilateral internuclear ophthalmoplegia. The authors describe a previously unrecognized association between the one-and-a-half syndrome and oculopalatal myoclonus (OPM)., Methods: Five clinical cases are presented, with pertinent physical findings and radiologic studies., Results: A previously unrecognized association of the one-and-a-half syndrome with subsequent development of OPM appears to exist. Involvement of the facial nerve in patients with the one-and-a-half syndrome may be a predictor of the subsequent development of OPM., Conclusion: Patients with the one-and-a-half syndrome and facial nerve palsy should be followed closely for possible future development of OPM.

Over the last 5 years the Pediatric Neurology service at King Faisal Specialist Hospital and Research Centre (KFSH&RC) has seen 131 infants and children with movement disorders. Forty-nine (37%) had identifiable biochemical defects, 25 of which were organic acidemias. Nineteen of 29 patients with dystonia had organic acidemias, primarily glutaric aciduria type 1 (7 patients), bilateral striatal necrosis (4 patients), and 3-methyl glutaconic aciduria (3 patients). All patients with parkinsonian rigidity (n = 11) had organic acidemias; again, the greatest number accounted for by glutaric aciduria type 1 (7 patients), who had both parkinsonian rigidity combined with dystonia. Myoclonus occurred in only 1 of 25 and chorea in 7 of 25 patients with organic acidemias. At the least all patients had bilateral lesions of putamen and head of caudate, seen best in MRI brain scans as increased T2 signal intensities with normal volume, and later with volume loss.

We have previously reported that rats exhibited audiogenic myoclonus at 3 days after cardiac arrest. This phenomenon peaked at 14 days, gradually tapered off at older ages, and disappeared in most rats by 60 days following cardiac arrest. Because treatment with the 5-HT2-selective agonist, (+/-)-1-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI) significantly attenuated audiogenic myoclonus in these postcardiac-arrest rats, the involvement of 5-HT2 receptors in posthypoxic stimulus-sensitive myoclonus was suggested. In the current study, we, therefore, examined the binding properties of 5-HT2 receptors in the rat bain at various time points following cardiac arrest. The affinity constant of [3H]ketanserin binding to 5-HT2 receptors in cortical membranes of rats did not change. In contrast, Bmax values were found to be reduced at 3 and 14 days after cardiac arrest with some recovery after 60 days. Taken together with previous results, these results indicate that hypoactivity of central 5-HT2 neurotransmission may underlie the development of posthypoxic stimulus-sensitive myoclonus in rats.

Chronic treatment of humans with several drugs is associated with lesions resembling lipidosis in different tissues. Recently, a Creutzfeldt-Jacob-like syndrome has been observed during tricyclic antidepressant therapy, but no evidence of interaction of these drugs with lysosomal function has been reported during such treatment. We report a case of dementia, myoclonus, peripheral neuropathy, and lipid storage in the skin due to antidepressant drug therapy, in which the discontinuation of drugs resulted in an improvement of clinical and electrophysiologic signs together with reduction of morphological evidence of lipid lysosomal storage.

A kindred in which at least 11 individuals in 3 consecutive generations have continuous muscle movement, i.e., myokymia, and periodic ataxia, has been studied. Three patients, a 24-year-old woman, her 4-year-old son and her 27-year-old sister, have been studied in detail. The disorder is inherited as an autosomal-dominant trait and presents in early childhood with attacks of ataxia of 1-2 min in duration, with associated jerking movements of the head, arms and legs. Attacks are provoked by abrupt postural change, emotional stimulus, and caloric-vestibular stimulation. At the age of 12 years approximately, facial and extremity myokymia appears. Physical findings include large calves, normal muscle strength and widespread myokymia of face, hands, arms and legs with a hand posture resembling carpopedal spasm. EMG studies at rest showed continuous spontaneous activity of otherwise normal motor units. Nerve conduction velocities were normal. Gastrocnemius biopsy in 2 patients showed fiber type grouping and small angular fibers, and was consistent with denervation. Histographic analysis of the biopsies demonstrated enlargement of both fiber types, particularly of Type I fibers. These findings are consistent with chronic denervation and an abnormality of motor neuron population or firing. The myokymia described here is of interest not only because of its genetic association with a movement disorder, but also because the muscle findings support a peripheral basis for the muscle movements.

A 55-year-old man is presented who developed severe multifocal myoclonus and tonic clonic seizures in his early thirties, and progressive limb weakness in his mid forties, when a ragged red fibre myopathy was diagnosed. He went on to develop a distal motor neuropathy and respiratory failure. Respiratory function tests indicated respiratory failure secondary to respiratory muscle weakness and a central hypoventilation syndrome. CT scan revealed brain stem atrophy and brain stem evoked responses were abnormal. A sural nerve biopsy showed severe axonal degeneration. Cytochrome difference spectra and polarographic studies on isolated intact muscle mitochondria were normal. This study reports the association of respiratory failure and sleep apnoea with Fukuhara's syndrome and presents biochemical data suggesting that the mitochondrial respiratory chain may be intact in some patients with this syndrome.