Mai Tsuchiya

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.

Multiple pseudofractures due to Fanconi’s syndrome associated with Wilson’s disease

We report a 40-year-old man who presented with multiple bone pseudofractures after about 20 years from the onset of Wilsons disease (WD). At age 36, he first noticed pain in his left shoulder. At age 39, he had multiple chest pain. On neurologic examinations, dysarthria and dysphagia due to pseudobulbar palsy, rigidity and tremor on right upper lim were observed. WD was confirmed because of low levels of plasma cupper and ceruloplasmin in addition to ATP7B gene mutation. The chest X-ray revealed multiple fractures of the several ribs. We diagnosed osteomalacia due to Fanconis syndrome because of hypophosphatemia and the impairment of renal tubules for WD. After administration of vitamin D, there happened no new bone pseudofractures. Although bone pseudofractures accompanied by Wilsons disease generally happen in childhood, we should be aware of this symptom even in adulthood.

Exome Sequencing Reveals a Novel Homozygous Frameshift Mutation in the CYP7B1 Gene in a Japanese Patient with SPG5

SPG5 is a rare subtype of autosomal recessive hereditary spastic paraplegia caused by a homozygous mutation in the oxysterol 7α-hydroxylase gene, CYP7B1. We describe the first Japanese patient with SPG5 with a novel mutation in the CYP7B1 gene. On exome sequencing, we identified a homozygous frameshift mutation, c.741delA, p.K247fs, in exon 3 of the CYP7B1 gene. The patient showed spastic paraparesis with white matter hyperintensities in the bilateral corona radiata and periventricular and subcortical regions on brain magnetic resonance imaging. The present study expands the mutation spectrum of CYP7B1 and provides an opportunity to study the genotype-phenotype correlation in SPG5.

A case of local tetanus presenting spastic paraplegia mimicking myelitis

A 35-year-old male was admitted to our hospital because of suspected myelitis. T2-weighted spinal MRI revealed a high intensity area at Th7-9. On admission, he showed mild weakness of the lower extremities and hyperreflexia of all extremities. Therefore, he was diagnosed with having spastic paraplegia. He presented no trismus or opisthotonos. There was pleocytosis in the cerebral spinal fluid. Dysuria, constipation and spasticity of the bilateral legs worsened, even though we administered methylprednisolone pulse therapy. Nonetheless, the symptoms had progressed on the 11th hospital day, opisthotonus and optic hyperesthesia were presented. On the 13th hospital day, we suspected local tetanus and administered tetanus toxoid. After one month, his symptoms had gradually improved. In the case of spastic paraplegia showing a subacute progression course and a faint abnormality on spinal MRI, the possibility of local tetanus should be considered.

Decreasing 123I-ioflupane SPECT accumulation and 123I-MIBG myocardial scintigraphy uptake in a patient with a novel homozygous mutation in the ZFYVE26 gene

Dear editor, Hereditary spastic paraplegia (HSP) is a group of neurodegenerative disorders characterized by weakness and spasticity of the lower extremities. HSP is divided into a pure form and a complicated one including mental retardation, ophthalmologic abnormalities, ichthyosis, cerebellar ataxia, thin corpus callosum, and extrapyramidal signs. In general, autosomal recessive HSP (ARHSP) tends to be the complicated form. In ARHSP, SPG11 is the most common type, SPG15 being the second. SPG11 and SPG15 overlap in clinical and brain MRI findings including spastic paraplegia associated with cognitive impairment, ophthalmologic abnormalities, thin corpus callosum, and leukodystrophy. I-ioflupane single-photon emission computed tomography (I-ioflupane SPECT) and I-metaiodobenzylguanidine myocardial scintigraphy (I-MIBG myocardial scintigraphy) are usually used for the diagnosis of Parkinson disease (PD) and Parkinson syndrome. Decreasing I-MIBG myocardial scintigraphy uptake indicates postganglionic sympathetic nerve denervation in a lot of diseases including Parkinson disease. To date, the I-ioflupane SPECT findings in SCA15 patients have rarely been reported, and no results of I-MIBG scintigraphy have been reported [1, 2]. We describe here a Japanese SCA15 patient with a novel homozygous ZFYVE26 mutation with decreasing I-ioflupane SPECT accumulation and IMIBG myocardial scintigraphy uptake. Case report

Sympathetic neurograms showing characteristics of both muscle and skin sympathetic nerve activity in a case with pure autonomic failure

We present sympathetic burst discharges that showed characteristics of both muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA) recorded in a case of pure autonomic failure (PAF). In September 2003, a 69-year-old man was admitted to our hospital because of frequent syncope and orthostatic dizziness for a year. On examination, he had a clear consciousness and normal cortical function (MMSE score of 29). Examination of the autonomic nervous system revealed significant orthostatic hypotension (OH). His supine BP was 142/86 mmHg (pulse rate was 73/min), and it decreased to 92/66 mmHg (pulse rate of 71/min) after standing for 3 min. He complained of decreased sweating on the face and trunk during summer for the last 3 years. He also complained of constipation and pollakiuria. Other neurological examinations revealed no abnormalities. Laboratory tests showed that the complete blood count, biochemical profile, electrocardiography (ECG), and cerebrospinal fluid parameters were all within normal limits. The coefficient of variation of the R–R interval on the ECG was 0.98% at rest (normal > 1.16% in persons over 40 years old). Assessment of nerve conduction and sensory evoked potentials demonstrated normal velocity and amplitude. Brain magnetic resonance imaging revealed mild brain atrophy consistent with the normal changes associated with aging. On cardiac MIBG scintigraphy, the H/M ratio was decreased (early image: 1.93; delayed image: 1.49). The plasma noradrenaline level was 210 pg/ml in the supine position and 310 pg/ml after standing. PAF was diagnosed from these findings. His OH-related symptoms were improved by treatment with midodrine hydrochloride (4 mg) and L-threoDOPS (300 mg). Sympathetic nerve activity (SNA) was elicited and recorded by microneurography according to the method and instruments described previously [1]. Detailed measurements and analysis are described in the Electronic supplementary material (ESM). Figure 1 displays representative recordings obtained from the patient at rest and while performing mental arithmetic (Fig. 1a) or the Valsalva maneuver (Fig. 1b). Although the resting frequency of SNA bursts showed a slight decrease when compared that of age/gender-matched healthy subjects at our institution (Table 1 in the ESM), an increased response of SNA bursts was confirmed during both mental Electronic supplementary material The online version of this article (http s://doi.org/10.1007 /s102 86-017-0497 -4) contains supplementary material, which is available to authorized users.

A case of Bickerstaff brainstem encephalitis with transient reflex myoclonus

A 33-year-old woman was admitted due to disturbance of consciousness, dysarthria, dysphagia, sensory disturbances and weakness of the left upper limb after mycoplasma infection. She was treated with intravenous immunoglobulin and intravenous high-dose methylprednisolone as Bickerstaff brainstem encephalitis (BBE). On the 15th hospital day, reflex myoclonus appeared on her face, neck, body and limbs induced by techniques of jaw jerk reflex and patellar tendon reflex. The myoclonus was disappeared after two weeks in accordance with improvement of BBE. The transient reflex myoclonus may be originated from brainstem lesion which was affected by BBE. Reflex myoclonus is thought to be rare symptom in patient with BBE.

Pre- and postganglionic vasomotor dysfunction causes distal limb coldness in multiple system atrophy

BACKGROUND The detailed pathophysiology of limb coldness in multiple system atrophy (MSA) is unknown. METHODS We evaluated cutaneous vasomotor neural function in 18 MSA patients with or without limb coldness, and in 20 healthy volunteers as controls. We measured resting skin sympathetic nerve activity (SSNA) and spontaneous changes of the sympathetic skin response (SSR) and skin blood flow (skin vasomotor reflex: SVR), as well as SVR and reflex changes of SSNA after electrical stimulation. The parameters investigated were the SSNA frequency at rest, amplitude of SSNA reflex bursts, absolute decrease and percent reduction of SVR, recovery time, and skin blood flow velocity. RESULTS Both the resting frequency of SSNA and the amplitude of SSNA reflex bursts were significantly lower in the MSA group than the control group (p<0.001 and p<0.05, respectively). There were no significant differences between the two groups with regard to the absolute decrease or percent reduction of SVR volume. The recovery time showed no significant difference between all MSA patients and control groups, but it was significantly prolonged in six MSA patients with limb coldness compared with that in the control group and that in MSA patients without limb coldness (p<0.01). The skin blood flow velocity was significantly slower in the MSA group than in the control group (p<0.001). CONCLUSION In MSA patients, limb coldness might occur due to impairments of the peripheral circulation based on prolongation of vasoconstriction and a decrease of skin blood flow velocity secondary to combined pre- and postganglionic skin vasomotor dysfunction.

No relation between sympathetic outflow to muscles and respiratory function in amyotrophic lateral sclerosis

OBJECTIVE In amyotrophic lateral sclerosis (ALS), not only impairment of motor neurons but also impairment of the autonomic nervous system has been demonstrated by previous physiological studies. Several investigators have reported a correlation between autonomic dysfunction and respiratory dysfunction in ALS. This study analyzed the relation between parameters of respiratory function and muscle sympathetic nerve activity (MSNA) in a large number of ALS patients. METHODS In 50 patients with ALS (mean age (SD): 62.1 (11.7) years), MSNA, heart rate (HR), and blood pressure (BP) were recorded simultaneously. The arterial oxygen content (PaO2), arterial carbon dioxide content (PaCO2), and forced vital capacity expressed as a percentage of the predicted value for healthy controls (%VC) were determined as parameters of respiratory function. RESULTS There were no significant correlations between MSNA and PaO2, PaCO2, %VC, or the disability score. Analysis of chronological changes in 14 patients examined twice showed that the disability score and PaCO2 were significantly increased, and %VC was significantly more decreased at the second examination compared with the first examination (p<0.01 and p<0.05, respectively). In contrast, HR, BP, burst rate of MSNA, and age-adjusted MSNA exhibited no significant changes between the first and second examinations. CONCLUSIONS These findings show that gradual deterioration of respiratory function in ALS patients is not associated with changes of quantitative MSNA parameters, which may suggest that abnormality of the autonomic nervous system is a primary feature of ALS.