Kunihiko Araki

Clinicopathological features of adult-onset neuronal intranuclear inclusion disease

Neuronal intranuclear inclusion disease (NIID) has highly variable clinical manifestations. Sone et al. describe the clinical and pathological features of 57 adult-onset cases diagnosed by postmortem dissection/antemortem skin biopsy. They report ‘dementia dominant’ and ‘limb weakness’ subtypes, and recommend consideration of NIID in the differential diagnosis of leukoencephalopathy and neuropathy.

Bidirectional neural connectivity between basal temporal and posterior language areas in humans

OBJECTIVE The basal temporal language area (BTL) is known to be involved in the semantic processing of language. To investigate the neural connectivity between BTL and the posterior language area (PL), we used cortico-cortical evoked potential (CCEP) technique. METHODS Four patients with intractable epilepsy who underwent presurgical evaluation with subdural electrodes were examined. All patients were right-handed and left language dominance by Wada test. We directly stimulated 20 pairs of electrodes placed on BTL in patient 1-3, putative BTL in patient 4, and PL in patient 1-4. In patient 4, all electrodes on the left temporal basal area were stimulated. RESULTS We could record 132 CCEP responses including 40 responses by the left basal temporal stimulation in patient 4. The waveforms from PL to BTL were triphasic, while those from BTL to PL were biphasic. The mean latency of the first negative peak (N1) was shorter at BTL (31.8-41.0ms; mean 35.1ms) than at PL (39.6-73.2ms; mean 52.3ms). CONCLUSIONS We revealed the uneven bidirectional connection between BTL and PL. SIGNIFICANCE We speculated that the two language areas are connected mainly through subcortical fibers from PL to BTL and through cortico-cortical fibers from BTL to PL, mediated by multisynaptic transmissions.

Mesial temporal lobe epilepsy with no specific histological abnormality: A distinct surgically remediable syndrome

PURPOSE The purposes of the study were twofold: to clarify the clinical features and surgical outcome of mesial temporal lobe epilepsy (MTLE) with no specific histological abnormality and to determine the optimal surgical strategy. METHODS Twelve patients who met the following criteria were included: (1) normal preoperative MRI; (2) intracranial EEG findings consistent with mesial temporal onset of seizures; (3) selective amygdalohippocampectomy (AHE) was performed, and the patient was followed for more than 2years postoperatively; and (4) hippocampal histopathology was nonspecific. Clinical characteristics, intracranial EEG findings, and postoperative seizure outcome were examined. These twelve patients were compared with twenty-one patients with MTLE with unilateral hippocampal sclerosis (HS) on MRI who underwent intracranial EEG before resection (control group). RESULTS In patients with MTLE with no specific histological abnormality, the age at onset was significantly higher, the history of febrile seizures was significantly less frequent, and preoperative IQ score was significantly higher than that in the control group. The proportion of patients with bitemporal independent and/or nonlateralizing seizure onset on intracranial EEG was 50% in patients with MTLE with nonspecific histopathology and was significantly higher than that in the control group. Seizure outcome was classified as Engel class I in seven patients, class II in three, class III in one, and class IV in one. Seizure outcome was favorable even in three patients with seizures originating more frequently from the side contralateral to the resected side. CONCLUSIONS Mesial temporal lobe epilepsy with no specific histological abnormality is a clinical entity distinctly different from MTLE with HS. Bitemporal independent and/or nonlateralizing seizure onset on intracranial EEG is very common. Although the presence of lateral temporal and/or extratemporal epileptogenicity should always be kept in mind, postoperative seizure outcome after AHE is favorable even in cases with bitemporal independent and/or nonlateralizing seizure onset.

Progressive supranuclear palsy and Parkinson's disease overlap: A clinicopathological case report

We describe a woman with a 13‐year history of postural instability, vertical gaze palsy and dopa‐responsive parkinsonism ‐ a clinical profile that corresponds to progressive supranuclear palsy (PSP) and Parkinsons disease (PD). The patient died at the age of 82 years. Neuropathological features included neuronal loss and gliosis in the substantia nigra, locus ceruleus, dorsal motor nucleus of the vagus, thoracic intermediolateral nucleus and nucleus basalis of Meynert, in addition to the typical pathology of PSP. Immunohistochemical studies demonstrated that PSP‐tau pathology was localized in the central nervous system, but Lewy body‐related α‐synucleinopathy was extensive in the central and peripheral nervous systems. Although PSP and PD may represent independent processes, this case could provide insight into a common defect in either protein phosphorylation or the proteinase surveillance system that contributes to human aging.

Myotonia-like symptoms in a patient with spinal and bulbar muscular atrophy

We describe the case of a 33-year-old man with a 4-year history of worsening muscle stiffness and weakness in his right hand. He showed elevated serum creatine kinase levels at the onset of muscle stiffness that was characterized by delayed muscle relaxation after voluntary contraction. This symptom often occurred during cold exposure, and was partially attenuated by sodium channel blockade. Electrodiagnostic findings in repetitive nerve stimulation, short-exercise, and cooling tests were normal. Electromyography showed chronic denervation potentials in his cranial, cervical, thoracic, and lumbosacral myotomes without myotonic discharge. He exhibited facial and tongue fasciculations, hypernasality, gynecomastia, neurogenic changes in muscle biopsy, and increased serum testosterone levels. Spinal and bulbar muscular atrophy (SBMA) was diagnosed on the basis of the CAG trinucleotide expansion in the gene coding androgen receptor. A myotonia-like symptom without myotonic discharge may present as an early neurological sign of SBMA, which possibly reflects a sodium channel dysfunction in skeletal muscles.

Acute Unilateral Isolated Oculomotor Nerve Palsy in an Adult Patient with Influenza A

An otherwise healthy 44-year-old woman exhibited isolated unilateral oculomotor nerve palsy accompanied by an influenza A infection. An intra-orbital MRI scan revealed that her right third intracranial nerve was enlarged and enhanced. She recovered completely during the first month after treatment with oseltamivir phosphate. Although intracranial nerve disorders that result from influenza infections are most frequently reported in children, it is noteworthy that influenza can also cause focal intracranial nerve inflammation with ophthalmoparesis in adults. These disorders can be diagnosed using intra-orbital MRI scans with appropriate sequences and through immunological assays to detect the presence of antiganglioside antibodies.

Serial magnetic resonance angiography in a patient with angioinvasive aspergillosis

Angioinvasive aspergillus can lead to acute infarction. A 74‐year old man complained about mild weakness of the left limbs; based on diffusion‐weighted magnetic resonance imaging, he was diagnosed with acute infarction in the right caudate and anterior limb of the internal capsule. After admission, he had a fever with disturbance of consciousness. Elevated serum β‐D‐glucan, elevated galactomannan antigen titers in cerebrospinal fluid and histopathological analysis on a biopsy specimen of the right sphenoid sinus enabled a diagnosis of Aspergillus infection. Serial magnetic resonance angiography showed the progressing stenosis of the major cerebral artery by angioinvasive aspergillosis with the spread of the cerebral infarction. Our case suggests that serial magnetic resonance angiography might be useful for monitoring progression of aspergillus vasculopathy.

Memory Loss and Frontal Cognitive Dysfunction in a Patient with Adult-onset Neuronal Intranuclear Inclusion Disease

Neuronal intranuclear inclusion disease (NIID) is an uncommon progressive neurodegenerative disorder. Adult-onset NIID can result in prominent dementia. We herein describe the case of a 74-year-old man who presented with dementia, cerebellar ataxia, neuropathy, and autonomic dysfunction. Diffusion-weighted imaging showed hyperintensity of the corticomedullary junction. Fluid-attenuated inversion recovery images showed frontal-dominant white matter hyperintensity. NIID was diagnosed from the presence of intranuclear inclusions in a skin biopsy sample. Neuropsychological testing revealed memory loss and frontal cognitive dysfunction, especially in relation to language and executive functions. We were therefore able to confirm the association of NIID with cognitive dysfunction.

Extensive cortical spongiform changes with cerebellar small amyloid plaques: the clinicopathological case of MV2K+C subtype in Creutzfeldt-Jakob disease.

We report a clinical case report of the MV2K+C subtype of sporadic Creutzfeldt‐Jakob disease (sCJD). The patient was a 72‐year‐old woman who exhibited progressive dementia over the course of 22 months. Diffusion‐weighted MRI during this period showed abnormal hyperintensity in the cerebral cortex in the early stage. The clinical course was similar to that of previously reported patients with the MV2K or MV2K+C subtype of sCJD. However, histopathological examination revealed unique features: severe extensive spongiform changes with perivacuolar deposits in the cerebrum and basal ganglia, plaque‐like PrP deposits in the cerebrum, and only mild changes in the cerebellum with small amyloid plaques (∼20 μm in diameter), smaller than those in the MV2K subtype or variant CJD (40–50 μm in diameter). Molecular analysis showed a methionine/valine heterozygosity at codon 129 and no pathogenic mutation in the PrP gene (PRNP). Western blot analysis of the protease‐resistant PrP (PrPSc) in the right temporal pole revealed the type 2 pattern, which is characterized by a single unglycosylated band, in contrast to the doublet described for the typical MV2 subtype of sCJD. The other intermediate band might exist in the cerebellum with kuru plaques. Therefore, small amyloid plaques in the cerebellum can be crucial for MV2K+C subtype.

Mirtazapine treatment ceased the progression of progressive multifocal leukoencephalopathy associated with systemic sarcoidosis

Progressive multifocal leukoencephalopathy occurs almost exclusively in immunosuppressed individuals. Mirtazapine, a 5‐hydroxytryptamine‐2A antagonist, has been used empirically against progressive multifocal leukoencephalopathy. A 60‐year‐old man who was diagnosed with sarcoidosis at 20 years‐of‐age and had not taken immunosuppressive therapies developed dysarthria, left hemiparesis and dressing apraxia. Cranial ?uid‐attenuated inversion‐recovery magnetic resonance imaging showed hyperintense areas in the right frontal and temporoparietal white matter. The initial diagnosis was neurosarcoidosis, based on non‐caseating granuloma in a lymph node biopsy. Immunosuppressive therapy was initiated; however, this aggravated his neurological symptoms. Immunohistochemistry of the brain biopsy showed John Cunningham virus infected large ballooned oligodendrocytes, leading to a diagnosis of progressive multifocal leukoencephalopathy. Treatment with mirtazapine improved the neurological symptoms, and the magnetic resonance imaging abnormality did not progress. We stress the diagnostic difficulties of distinguishing progressive multifocal leukoencephalopathy from neurosarcoidosis, and suggest that mirtazapine treatment is effective against progressive multifocal leukoencephalopathy associated with sarcoidosis.