Intracranial vascular calcification with extensive white matter changes in an autopsy case of pseudopseudohypoparathyroidism.

We herein report an autopsy case of a 69-year-old man with pseudopseudohypoparathyroidism. The patient suffered from mental retardation and spastic tetraparesis and had all the features of Albright's hereditary osteodystrophy with a normal response to parathyroid hormone in the Ellsworth-Howard test. Computed tomography demonstrated symmetrical massive brain calcification involving the bilateral basal ganglia, thalami, dentate nuclei and cerebral gray/white matter junctions, which was consistent with Fahr's syndrome. Magnetic resonance imaging revealed extensive white matter changes sparing the corpus callosum. Severe ossification of the posterior longitudinal ligament of the cervical spine was also demonstrated. A neuropathological examination revealed massive intracranial calcification within the walls of the blood vessels and capillaries with numerous calcium deposits. The calcium deposits aligned along the capillaries, and deposits in the vessel wall at the initial stage were confined to the border between the tunica media and adventitia. The vascular calcification in the basal ganglia continuously spread over the surrounding white matter into the cortex. The area of vascular calcification in the white matter was very well correlated with the area of the attenuated myelin staining. Axonal loss, myelin sheath loss and gliosis were observed in the white matter with severe vascular calcification. We should recognize the continuous area of vascular calcification and its correlation with extensive white matter changes as possible causes of neuropsychiatric symptoms in pseudopseudohypoparathyroidism with Fahr's syndrome.

An autopsy case of hemiconvulsion-hemiplegia-epilepsy syndrome manifesting as cerebral hemiatrophy in an elderly man.

We report an autopsy case of hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome in a 79-year-old man. HHE syndrome usually occurs in children younger than 4 years of age. Although most HHE syndrome patients live into adult life, only a few cases of the syndrome have been reported in the elderly. In our case, cerebral hemiatrophy, left mesial temporal sclerosis and crossed cerebellar atrophy were observed. Because this is the oldest case ever reported, we further investigated age-related neuropathological changes and found an interhemispheric difference in amyloid-ß-related neuropathologic changes. There were almost no senile plaques or amyloid-laden vessels in the left hemisphere. As far as we know, this is the first report of age-related neuropathology in a brain manifesting HHE syndrome.

Gerstmann-Straeussler-Scheinker disease with P102L prion protein gene mutation presenting with rapidly progressive clinical course.

We describe an autopsied case of a Japanese woman with Gerstmann-Straeussler-Scheinker disease (GSS) presenting with a rapidly progressive clinical course. Disease onset occurred at the age of 54 with dementia and gait disturbance. Her clinical course progressively deteriorated until she reached a bedridden state with myoclonus 9 months after onset. Two months later, she reached the akinetic mutism state. Nasal tube feeding was introduced at this point and continued for several years. Electroencephalograms showed diffuse slowing without periodic sharp-wave complexes. Diffusion-weighted magnetic resonance imaging (MRI) showed widespread cerebral cortical hyperintensity. Prion protein (PrP) gene analysis revealed a Pro to Leu point mutation at codon 102 with methionine homozygosity at codon 129. The patient died of respiratory failure after a total disease duration of 62 months. Neuropathologic examination revealed widespread spongiform change with numerous eosinophilic amyloid plaques (Kuru plaques) in the cerebral and cerebellar cortices by H & E staining. Diffuse myelin pallor with axon loss of the cerebral white matter, suggestive of panencephalopathic-type pathology was observed. Numerous PrP immunopositive plaques and diffuse synaptic-type PrP deposition were extensively observed, particularly in the cerebral and cerebellar cortices. Western blot analysis of proteinase Kresistant PrP showed a characteristic band pattern with a small molecular band of 6 kDa. The reason for the similarity in clinicopathologic findings between the present case and Creutzfeldt-Jakob disease is uncertain; however, the existence of an unknown disease-modifying factor is suspected.

Bilateral reversible optic neuropathy as the first sign of Waldenström macroglobulinema.

Objective: To report a case of bilateral reversible optic neuropathy as the first sign of Waldenström macroglobulinemia (WM). Methods: Observational case report. Results: A 52-year-old man had a sudden loss of vision in the left eye. Examinations revealed the presence of a serum monoclonal immunoglobulin (IgM kappa) in the serum. Even after a session of steroid pulse therapy, optic neuropathy became bilateral and then resolved almost completely after 4 months. The condition progressed to WM with multiorgan lesions years later. There was no evidence of optic neuropathy recurrence. The literature revealed two cases of monoclonal gammopathy (MG): a 64-year-old man with multiple myeloma (MM) with IgA lambda and a 51-year-old man with MM with IgG kappa. These cases have similar conditions: 1) visual reduction as an initial symptom of MG, 2) bilateral involvement, 3) no sign of central nervous system (CNS) infiltration shown by normal brain magnetic resonance images, and 4) recovery to a visual acuity of ≥1.0 bilaterally with no reoccurrence. The excessive Igs or B-cell hyperactivity may activate an autoimmune mechanism that reversibly interferes with the bilateral optic nerves. Conclusion: Bilateral optic neuropathy was the initial symptom of WM. There was no evidence of CNS infiltration; it recovered and then did not reoccur. The pathogenesis remained unknown, but two cases of MG were reported in the literature with remarkably similar conditions.

An Autopsy Confirmed Neuromyelitis Optica Spectrum Disorder with Extensive Brain White Matter Lesion and Optic Neuritis but Intact Spinal Cord, Clinically Mimicking a Secondary Progressive Multiple Sclerosis-like Course.

A 57-year-old woman presented with optic neuritis with repeated clinical symptoms of focal demyelination of the cerebral white matter and brain stem for 14 years. At the end of the patient's course, the clinical signs mimicked secondary progressive multiple sclerosis, but whether it was caused by interferon administration or neuromyelitis optica spectrum disorders (NMOSD) - or a combination of both or others - was unclear. Histopathological findings indicated the etiology to be NMOSD, with no apparent plaque in spinal cord specimens. This case suggests that an accurate clinical diagnosis requires serum anti-aquaporin 4 antibody measurements as well as an autopsy examination.

Subjective assessment of effectiveness, quality of life, and psychological status of patients receiving botulinum toxin therapy for hemifacial spasm, blepharospasm, or cervical dystonia.

OBJECTIVES: Evaluations of subjective effectiveness, quality of life (QOL), and mental status of patients receiving treatment with botulinum toxin (BTX) for hemifacial spasm (FS), blepharospasm (BS), and cervical dystonia (CD) were conducted using a self-administered questionnaire. METHODS: Eighty-eight patients who received BTX treatment in the stable stage were analyzed. A numerical rating scale was used to assess treatment effectiveness, home QOL, and social QOL. Anxiety and depression were examined using the hospital anxiety and depression scale. RESULTS: In men, the treatment effectiveness was 2.1±1.0 for FS patients, 2.8±0.5 for BS patients, and 4.0±2.0 for CD patients, which indicates that FS was more effectively treated than CD. QOL scores were higher and anxiety and depression scores were lower in FS patients than BS and CD patients. Overall, social QOL scores were lower than home QOL. A high prevalence ratio of depression was found in BS and CD patients. CONCLUSIONS: CD responded less effectively to BTX compared with FS and BS. Additionally, FS and BS patients exhibited similar treatment effects. All of these disorders affect the patient's appearance, which can reduce self-esteem and social QOL and potentially cause anxiety and depression. BS and CD patients exhibited a higher prevalence of depression than FS patients, which indicates a relationship with the underlying mechanisms of dystonia. Asking patients about subjective effectiveness, QOL, and psychiatric status can help staff respond to patient issues.

Clinical study on the cerebral infarction accompanied with septic disseminated intravascular coagulation.

OBJECTIVES: Patients with disseminated intravascular coagulation (DIC) due to sepsis often develop cerebral infarction; but the frequency, mechanism of onset and prognosis have not been fully elucidated. We reported courses and characteristics of septic DIC cases hospitalized in our hospital in the present study. METHODS: Patients with septic DIC who underwent brain imaging were selected. Vital signs, disorders of consciousness and blood test results at the time of onset were compared between cases that developed cerebral infarction (cerebral infarction group) and those that did not (non-infarction group).In cases of cerebral infarction, the site and the size of the infarct lesion were also described. RESULTS: In 27 septic DIC patients who underwent brain imaging, eight patients had cerebral infarction. Although the percentage of patients who survived in the cerebral infarction group (2/8, 25%) was lower than that in the non-infarction group (7/17, 37%), , no significant difference was observed as both group showed poor prognoses. Those two patients who survived in the cerebral infarction group had severe consciousness disturbance and poor functional prognosis. Although the body temperature was significantly lower and the blood pressure was higher in the cerebral infarction group, no significant difference was found in general blood tests, so we thought it would be necessary to look for other markers that could be indicators for the risk of cerebral infarction.In the cerebral infarction group, two cases had a single lesion, and six cases had multiple lesions. Of the latter, two cases had massive lesions with a diameter of 1.5 cm or greater, four cases had only small lesions with a diameter of less than 1.5 cm, and two cases had a mixture of both. Most of the patients had lesions in the vertebrobasilar artery, which suggested that the pathogenesis involves not only embolism due to microthrombi, but also vasculitis and intravascular inflammation. CONCLUSIONS: Cerebral infarction was observed highly frequently; eight out of 27 cases (29.6%) when brain imaging was undergone in septic DIC patients. The prognosis of patients with cerebral infarction was poor, but no difference from the non-infarction group was observed. In addition to embolism, the presence of inflammation is considered to be important for the onset. In order to predict the prognosis and determine a suitable treatment, it would be recommended to undergo brain imaging when patients with septic DIC have consciousness disturbance or elevated blood pressure, and do not have fever.

Clinical investigation in non-liver cirrhosis portosystemic shunt encephalopathy-four case series.

We reported here four cases presenting with disturbance of consciousness over long periods of time and hyperammonemia. Two patients were on maintenance hemodialysis. Contrast-enhanced computed tomography (CT) of abdomen and balloon-occluded retrograde contrast venography revealed existence of a non-cirrhotic portosystemic shunt. Conservative treatment such as intravenous branched-chain amino acid administration and oral lactulose administration had only a modest effect in all patients. Improvements in symptoms were observed following the occlusion of the shunt path in three patients. Measurements of ammonia values would be the most important test for screening, but changes in Fischer's ratio or indocyanine green (ICG) test values were also correlated with clinical symptoms. Neurologists should keep in mind the possibility of non-cirrhotic portosystemic shunts when they encounter patients with disturbance of consciousness. They should also remember that occlusion of the shunt pathway is an effective treatment.

The identified clinical features of Parkinson's disease in homo-, heterozygous and digenic variants of PINK1.

To investigate the prevalence and genotype-phenotype correlations of phosphatase and tensin homolog induced putative kinase 1 (PINK1) variants in Parkinson's disease (PD) patients, we analyzed 1700 patients (842 familial PD and 858 sporadic PD patients from Japanese origin). We screened the entire exon and exon-intron boundaries of PINK1 using Sanger sequencing and target sequencing by Ion torrent system. We identified 30 patients with heterozygous variants, 3 with homozygous variants, and 3 with digenic variants of PINK1-PRKN. Patients with homozygous variants presented a significantly younger age at onset than those with heterozygous variants. The allele frequency of heterozygous variants in patients with age at onset at 50 years and younger with familial PD and sporadic PD showed no differences. [123I]meta-iodobenzylguanidine (MIBG) myocardial scintigraphy indicated that half of patients harboring PINK1 heterozygous variants showed a decreased heart to mediastinum ratio (12/23). Our findings emphasize the importance of PINK1 variants for the onset of PD in patients with age at onset at 50 years and younger and the broad spectrum of clinical symptoms in patients with PINK1 variants.

An Adult Case of Generalized Convulsions Caused by the Ingestion of Ginkgo biloba Seeds with Alcohol.

A 64-year-old woman developed symptoms of vomiting and tonic-clonic convulsions 9.5 h after eating 50 roasted Ginkgo biloba seeds with 100 g of alcohol. The intravenous administration of pyridoxal phosphate effectively improved the symptoms. Blood samples were collected and stored over 35 h. The assessment of 4'-O-methylpyridoxine and vitamin B6 vitamers indicated high levels of both, but the pyridoxal phosphate levels were low during the acute stage. These results suggest that 4'-O-methylpyridoxine inhibits the transformation of vitamin B6 analogues to the active form, pyridoxal phosphate. In our case, alcohol may have extended the period until ginkgo intoxication appeared.

Dopaminergic function in spinocerebellar ataxia type 6 patients with and without parkinsonism.

BACKGROUND: Although pure cerebellar ataxia is usually emphasized as the characteristic clinical feature of spinocerebellar ataxia type 6 (SCA6), parkinsonism has been repeatedly described in patients with genetically confirmed SCA6. METHODS: We conducted a positron emission tomography study using a combination of [18F]fluoro-L-dopa for dopamine synthesis and [11C]raclopride for dopamine D2 receptor function on six genetically confirmed SCA6 patients, both with and without parkinsonism. To the best of our knowledge, this is the first dopamine receptor imaging study of patients with SCA6. RESULTS: Most patients had somewhat decreased dopaminergic function, and this decrease was significant in the caudate nucleus. In addition, one SCA6 patient with parkinsonism had whole striatal dysfunction of both dopamine synthesis and dopamine D2 receptor function. CONCLUSIONS: The pathology of SCA6 may not be restricted to the cerebellum, but may also be distributed across various regions, including in both presynaptic and postsynaptic dopaminergic neurons to some degree. Patients with SCA6 may show apparent parkinsonism after the progression of neurodegeneration.

[Pure agraphia with topographical disorientation caused by right hemisphere lesion].

A 69-year-old, right-handed, Japanese male patient presented with pure agraphia with topographical disorientation after hemorrhage in the right parietal lobe. Upon developing cerebral hemorrhage, he was referred to our hospital for close examination of agraphia. There was no paresis or clumsiness in his extremities. His speech was fluent and well-articulated. Neither aphasia nor reading impairments was found, although there was a clear writing impairment with effort and hesitation. His writing of both kanji and kana letters contained additional, absent or deformed strokes or parts. No hemianopia, prosopagnosia, constructional disturbances and dressing apraxia were found. He could recognize familiar buildings or landscapes, but often lost his way around well-known areas. MR images revealed subcortical lesions of precuneus, superior and inferior parietal lobules in the right hemisphere, around the posterior horn of the lateral ventricle. He revealed pure agraphia and topographical disorientation after the right brain haemorrhage, without dementia or personality change. These findings indicate that the right parietal lobe participates in the kinesthetic movements of writing. Some authers have been documented cases of aphasic agraphia or alexia with agraphia caused by right hemisphere damage in dextrals, but pure agraphia caused by the lesion in the right hemisphere is very rare.

Hypocretin-1 levels in the cerebrospinal fluid of patients with Percheron artery infarction with or without midbrain involvement: A case series.

BACKGROUND: Bilateral paramedian thalamic infarctions (BPTIs) due to artery of Percheron occlusion are known to cause hypersomnia. However, the role of hypocretin-1, a wake-promoting peptide that is located at the lateral hypothalamus, in hypersomnia in these patients remains unclear. METHODS: To clarify the role of hypocretin-1 in hypersomnia in patients with BPTIs, hypocretin-1 levels in the cerebrospinal fluid (CSF) were measured in 6 patients with BPTIs: 2 with rostral midbrain involvement (BPT+RMI) and 4 without midbrain involvement (BPT-MI). RESULTS: CSF hypocretin-1 levels were decreased in 2 patients with BPT+RMI and were within normal ranges in 4 patients with BPT-MI. Hypersomnia was noted in all the patients. In one BPT+RMI patient, hypersomnia was improved within 2 weeks and decreased CSF hypocretin-1 levels were reversed (acute phase (on day 9), 109.2 pg/mL; chronic phase (at 3 months), 323 pg/mL), whereas another BPT+RMI patient who displayed coma in the acute phase had decreased CSF orexin levels (107 pg/mL) at day 49 and exhibited severe disability. CONCLUSION: Hypocretin deficiency was not involved in hypersomnia observed in BPT-MI patients; however, CSF hypocretin-1 levels were reduced in BPT+RMI patients. Reduced CSF hypocretin-1 levels in the chronic phase may possibly predict a poor clinical outcome in patients with Percheron artery infarction.

Hemodialysis-related portal-systemic encephalopathy.

Hemodialysis-related portal-systemic encephalopathy (HRPSE) is characterized by the presence of portosystemic encephalopathy without liver dysfunction, usually caused by changes in the systemic venous flow related to hemodialysis. We herein describe the case of a 75-year-old woman who developed hepatic encephalopathy five years after the initiation of hemodialysis. Abdominal contrast-enhanced computed tomography (CT) and three-dimensional CT angiography revealed a portosystemic venous shunt, and the patient was diagnosed with portosystemic encephalopathy. Occlusion therapy ameliorated her disturbance of consciousness. HRPSE should be recognized as a treatable neuropsychiatric disorder.

Neurologic complications associated with influenza vaccination: two adult cases.

We describe two adult cases of neurologic complications occurring after influenza vaccination. The first case was a 62-year-old man who experienced convulsions 5 days after vaccination, and the second case was a 70-year-old man who exhibited paraplegia 7 days after vaccination. Diagnoses of acute disseminated encephalomyelitis and transverse myelitis with acute motor axonal neuropathy were made, respectively, and steroid pulse therapy and intravenous gamma globulin therapy alleviated the patients' symptoms. Although the efficacy and cost benefit of influenza vaccination have been widely accepted, such neurologic complications might occur in the elderly or even in adults.

[A case of meningoencephalitis and spondylodiscitis caused by Campylobacter fetus subsp. fetus infection].

Campylobacter fetus subsp. fetus (C. fetus) is a gram-negative, curved, rod-shaped microaerophile, occasionally may cause meningitis or meningoencephalitis in humans. This report documents the case of 49-year-old man with lumbar spondylodiscitis and meningoencephalitis caused by C. fetus infection. On admission, the patient was delirious and severe inflammatory reactions were seen in his serum. Cerebrospinal fluid (CFS) revealed normal glucose concentration and moderate mononuclear leukocytosis. Campylobacter species, which was very difficult to be identified, was cultured from the blood and CSF. During his clinical course, the patient complained of severe back pain, and lumbar MRI showed low intensity in a T1-weighed image of the L4 and L5 vertebral bodies and high intensity in a T2-weighed image of the L4-5 disc. The patient was diagnosed with spondylodiscitis caused by C. fetus infection. Meningoencephalitis may have occurred as a secondary infection. Antibiotics were administered, and the patient's condition improved. To our knowledge, only a few cases of spondylodiscitis caused by C. fetus have been reported. A CSF glucose concentration in the normal range and mononuclear leukocytosis are atypical findings in patients with pyogenic meningitis. Therefore, neurologists must be fully aware of the possible symptoms and signs of C. fetus infection.

[A probable case of Creutzfeldt-Jakob disease with electroretinogram alterations].

Although visual disturbance is recognized as a clinical feature of Creutzfeldt-Jakob disease (CJD), lesions within the retina have to date, recorded little attention. In this single case study, we report a case of retinopathy observed in a 72-year-old female patient with CJD. The patient admitted to the hospital complaining of a 2-month history of visual disturbance, dysarthria, and gait disorder. Electroencephalogram showed periodic synchronous discharges synchronizing with myoclonic jerks. Electroretinogram (ERG) using single bright flash in a dark-adapted state demonstrated the absence of b-wave in both eyes. One month later, ERG could no longer record a-wave of the right eye. The absence of b-wave on ERG indicated a disorder within the inner layer of the retina, furthermore lesions detected in the occipital lobe were considered too mild to have elicited such visual disorder. We further conclude that retinopathy may be found in CJD and can progress in retrograde from ganglion cells to photoreceptors. Although the frequency of retinopathy among the CJD population is unclear, detailed clinical observation and analysis of ERG in patients with visual disorders of unknown cause is extremely important for both the screening and exclusion of CJD.

Longitudinal study on MRI intensity changes of Machado-Joseph disease: correlation between MRI findings and neuropathological changes.

To disclose the neuropathological progression course of Machado-Joseph disease (MJD), magnetic resonance imaging (MRI) findings of six genetically confirmed MJD cases (four males and two females, including an autopsied female, all unrelated to one another) were further investigated on neurodegeneration. Brain MRI studies were repeated in all cases at different stages of the disease. Ages at the first MRI study ranged from 47 to 65 years (55.2 ± 7.1), with observation periods from 4.5 to 10.6 years (6.95 ± 2.48). We paid particular attention to two types of previously reported MRI findings detectable using T2-weighted images. One is located just outside the internal capsules, and another in the pons. A linear high-intensity change along the internal capsules was detected in all cases, and showed progression during the observation period. A comparison between MRI and autopsy findings suggested that the lesion might reflect degeneration with neuronal loss, astrocytosis, and gliosis in the internal segment of the globus pallidus. A cross-shaped high-intensity change in the pons was well advanced but still incomplete in all cases. In this region, pontine transverse fibers were atrophic, while longitudinal fibers remained intact. Pontine nuclei showed apparent nerve cell loss, and the remaining cells had many 1C2-positive intranuclear inclusions. Since these findings were detected both by lifetime images and by postmortem examination, MRI intensity changes could track the progression of neurodegeneration. Based on a comparison between MRI findings and neuropathology, the degeneration of an internal segment of the globus pallidus (one of the pathological features of MJD) had progressed following the initial symptoms.