High frequency of beta-propeller protein-associated neurodegeneration (BPAN) among patients with intellectual disability and young-onset parkinsonism.

Neurodegeneration with brain iron accumulation (NBIA) is a genetically heterogeneous disorder, characterized by the accumulation of iron in regions such as the basal ganglia. We enrolled 28 patients with childhood intellectual disability and young-onset parkinsonism (≤40 years at onset) and 4 patients with infantile neuroaxonal dystrophy. All had been clinically diagnosed, and the prevalence of genetic mutations linked to NBIA (PANK2 [exons 1-7], PLA2G6 [exons 2-17], C19orf12 [exons 1-3], WDR45 [exons 2-11], COASY [exons 1-9], FA2H [exons 1-7], and RAB39B [exons 1, 2]) was evaluated. We detected 7 female patients (25.0%, 7 of 28) with de novo heterozygote WDR45 mutations, which are known to be pathogenic for beta-propeller protein-associated neurodegeneration. All 7 patients had common clinical features. Pathogenic mutations in other NBIA genes were not found. We also screened 98 patients with early-onset parkinsonism without intellectual disability and 110 normal controls of Japanese origin for WDR45 mutations. None had WDR45 mutations. Our data suggest a high frequency of beta-propeller protein-associated neurodegeneration mutations in the Japanese population.

[Cervical retro-odontoid pseudo-tumor treated with posterior decompression surgery].

A cervical retro-odontoid pseudo-tumor, which is considered as a reactive fibrocartilaginous mass, is a rare condition in cervical myelopathy. A 63-year-old male, with repeated neck axial movements by a long-term leisure-time cycling, developed subacute myelopathy. Cervical MRI showed a mass lesion at the retro-odontoid region, compressing to the upper spinal cord. After detailed systemic and local examinations that ruled out primary or metastatic malignancy and inflammatory disorders such as rheumatoid arthritis or chronic kidney diseases, a retro-odontoid pseudo-tumor was diagnosed clinically. The patient underwent posterior C1-laminectomy without tumor resection and its pathological confirmation. After the surgery, his neurological signs of cervical myelopathy improved, and a follow-up MRI one year later showed a mild reduction of the tumor size. The neuro-physicians should recognize the relatively benign pseudotumor in cervical myelopathy, because the tumor size usually shows no further enlargement or regression only after decompression surgery without tumor resection.

[Endogenous endophthalmitis and meningo-encephalitis in septic bacteremia of Klebsiella pneumoniae].

Endogenous endophthalmitis may be a rare condition in acute meningo-encephalitis. A 69-year-old compromised adult abruptly developed septic bacteremia and meningo-encephalitis by Klebsiella pneumoniae. After an improvement from initial conscious disturbance and systemic inflammatory unstable vital conditions by treatment of intensive antibiotic medications, severe unilateral endogenous endophthalmitis with impaired visual acuity was diagnosed by detailed ophthalmological assessments and it deteriorated rapidly. After early vitreous surgery with anti-biotic direct injection, the patient successfully regained visual acuity of 20/200. Among the organisms of endogenous bacterial endophthalmitis, Klebsiella pneumoniae is the worst pathogen mostly resulting in vision loss or enucleation despite any aggressive treatments. The neuro-physicians should recognize the presence of refractory endophthalmitis by Klebsiella pneumoniae, even if clinically asymptomatic, because prompt ophthalmologic diagnosis and managements may improve the outcome.

Reversal of large ischemic injury on hyper-acute diffusion MRI.

Reversal of early ischemic injury on diffusion-weighted MRI (DWI) occurs rarely. In a stroke patient who abruptly developed stupor and left hemiparesis, DWI scanned 78 min after onset demonstrated a large ischemic injury in the right hemisphere with a DWI-ASPECTS (Albert Stroke Program Early Computed Tomography Score) of 5 points, although baseline brain CT was perfectly normal. MR angiography (MRA) showed an occlusion of the right middle cerebral artery trunk, and the patient received intravenous thrombolysis 105 min after onset. A second MRA 30 h later showed complete vessel recanalization, and DWI demonstrated a perfect reversal of the initial large ischemic injury, associated with very small thrombus-fragmented cortical surface infarctions. Outcome at 3 months was a modified Rankin Scale score of 0, and the fluid-attenuated inversion recovery image showed only a small final infarction at the cortical surface. Hyper-acute DWI-defined large ischemic injury may very rarely represent a nearly perfect reversible area, and it may be a therapeutic target.

[Three cases of small brain infarction in the lateral wall of the fourth ventricle presenting with paroxysmal positional vertigo and vomiting].

A lesion responsible for central paroxysmal positional vertigo (PPV) is often found in the dorsolateral wall of the fourth ventricle. A relatively large tumor or hemorrhage in the dorsolateral wall of the fourth ventricle usually causes central PPV, but small brain infarction has hardly been reported to cause central PPV. We report three cases of a small brain infarction in the lateral wall of the fourth ventricle presenting with central PPV. All of the cases showed similar clinical features in which a given recumbent position and a sitting position caused a dizziness associated with nausea and vomiting over an acute period. The symptom lasted one to two months after the onset. In two of our cases, no neurological abnormal signs, except nystagmus, were observed, and initial differentiation of central PPV from peripheral PPV was difficult. Interruption of the vestibular nuclei-archicerebellar loop seems to be responsible for the central PPV. Recognition of the clinical features of central PPV and diffusion-weighted MRI images are important for a precise local diagnosis in small brain infarction showing PPV.

Possible reduced penetrance of expansion of 44 to 47 CAG/CAA repeats in the TATA-binding protein gene in spinocerebellar ataxia type 17.

BACKGROUND: Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant cerebellar ataxia caused by expansion of CAG/CAA trinucleotide repeats in the TATA-binding protein (TBP) gene. Because the number of triplets in patients with SCA17 in previous studies ranged from 43 to 63, the normal number of trinucleotide units has been considered to be 42 or less. However, some healthy subjects in SCA17 pedigrees carry alleles with the same number of expanded repeats as patients with SCA17. OBJECTIVE: To investigate the minimum number of CAG/CAA repeats in the TBP gene that causes SCA17. DESIGN: We amplified the region of the TBP gene containing the CAG/CAA repeat by means of polymerase chain reaction and performed fragment and sequence analyses. PATIENTS: The subjects included 734 patients with SCA (480 patients with sporadic SCA and 254 patients with familial SCA) without CAG repeat expansions at the SCA1, SCA2, Machado-Joseph disease, SCA6, SCA7, or dentatorubral-pallidolluysian atrophy loci, with 162 healthy subjects, 216 patients with Parkinson disease, and 195 with Alzheimer disease as control subjects. RESULTS: Eight patients with SCA possessed an allele with more than 43 CAG/CAA repeats. Among the non-SCA groups, alleles with 43 to 45 repeats were seen in 3 healthy subjects and 2 with Parkinson disease. In 1 SCA pedigree, a patient with possible SCA17 and her healthy sister had alleles with 45 repeats. A 34-year-old man carrying alleles with 47 and 44 repeats (47/44) had developed progressive cerebellar ataxia and myoclonus at 25 years of age, and he exhibited dementia and pyramidal signs. He was the only affected person in his pedigree, although his father and mother carried alleles with mildly expanded repeats (44/36 and 47/36, respectively). In another pedigree, 1 patient carried a 43-repeat allele, whereas another patient had 2 normal alleles, indicating that the 43-repeat allele may not be pathologic in this family. CONCLUSIONS: We estimate that 44 CAG/CAA repeats is the minimum number required to cause SCA17. However, the existence of unaffected subjects with mildly expanded triplets suggests that the TBP gene mutation may not penetrate fully. Homozygosity of alleles with mildly expanded triplet repeats in the TBP gene might contribute to the pathologic phenotype.

[A case of adult-onset Huntington disease presenting with spasticity and cerebellar ataxia, mimicking spinocerebellar degeneration].

We report an adult-onset case of Huntington disease presenting with spasticity and cerebellar ataxia. The patient, a 47-year old woman, was admitted to our clinic because of progressive involuntary movements. Her elder brother suffered from the similar symptoms. Neurologically, she had quick temper, dementia, generalized chorea, spasticity and truncal ataxia. MRI demonstrated atrophy of caudate, midbrain, pons and cerebellum. From these clinical and MRI findings, she was suspected to have a form of spinocerebellar degeneration (SCD), particularly DRPLA. However, DNA analysis showed CAG repeats in huntington gene was expanded (47/20). Accordingly she was diagnosed as having adult-onset Huntington disease, mimicking SCD. This case indicates Huntington disease may present atypical clinical features and it is crucial to determine CAG repeat size in huntington gene for the patient with dementia and/or movement disorders, etiology of which is unknown. The relationships between clinical phenotypic variations and huntington gene expression are not determined.

[A case of slowly progressive unilateral spastic hemiparasis, hand clumsiness, limb ataxia and constructional apraxia].

A 65-year-old woman was seen in our clinic because of a 4-year history of slowly progressive left hand clumsiness and left limping. Neurologically, she had left-side spastic hemiparasis including her tongue, hand clumsiness, limb ataxia, constructional apraxia, and memory impairment. Dementia, parkinsonism and lower motor neuron sign were not confirmed. MRI study showed diffuse cerebral atrophy and shrinkage of the right cerebral peduncle and pontine base. SPECT (99mTc-ECD) study revealed hypoperfusion of the right fronto-parietal cortex. This is a rare case presented with slowly progressive left-side spastic hemiparasis, mimicking Mills' syndrome. In addition this case had other cortical signs, such as ipsilateral hand clumsiness, limb ataxia, constructional apraxia. Neuroimaging study suspects that the right front-parietal cortex is the primary lesion. Etiologically atypical motor neuron disease with adjacent cortical involvement is suspected rather than corticobasal degeneration with severe unilateral pyramidal tract degeneration.