Ultra-high-dose methylcobalamin in amyotrophic lateral sclerosis: a long-term phase II/III randomised controlled study.

OBJECTIVE: To evaluate the efficacy and safety of intramuscular ultra-high-dose methylcobalamin in patients with amyotrophic lateral sclerosis (ALS). METHODS: 373 patients with ALS (El Escorial definite or probable; laboratory-supported probable; duration ≤36 months) were randomly assigned to placebo, 25 mg or 50 mg of methylcobalamin groups. The primary endpoints were the time interval to primary events (death or full ventilation support) and changes in the Revised ALS Functional Rating Scale (ALSFRS-R) score from baseline to week 182. Efficacy was also evaluated using post-hoc analyses in patients diagnosed early (entered ≤12 months after symptom onset). RESULTS: No significant differences were detected in either primary endpoint (minimal p value=0.087). However, post-hoc analyses of methylcobalamin-treated patients diagnosed and entered early (≤12 months' duration) showed longer time intervals to the primary event (p<0.025) and less decreases in the ALSFRS-R score (p<0.025) than the placebo group. The incidence of treatment-related adverse events was similar and low in all groups. CONCLUSION: Although ultra-high-dose methylcobalamin did not show significant efficacy in the whole cohort, this treatment may prolong survival and retard symptomatic progression without major side effects if started early. TRIAL REGISTRATION NUMBER: NCT00444613.

Preventive Treatment with Lomerizine Increases Cerebral Blood Flows during the Interictal Phase of Migraine.

BACKGROUND: Changes in regional cerebral blood flow (rCBF) were reported in migraineurs. However, little is known how preventive medications of migraine can influence rCBF. Lomerizine, a calcium channel blocker, has been used for migraine prophylaxis in Japan. We examined rCBF after lomerizine treatment. SUBJECTS AND METHODS: Migraine was diagnosed according to the criteria of the International Classification of Headache Disorders, Third Edition beta. Migraine subtype was classified into migraine with aura (MA) and migraine without aura (MO). Lomerizine (10 mg/day, per oral) was administered for 3 months. Headache Impact Test-6 (HIT-6) and blood pressure (BP) were compared at baseline and end point. Brain single photon emission computed tomography using 99mTc-ethyl cysteinate dimer was performed at the interictal period. Brain SPECT data were analyzed according to revised version of 3-dimensional stereotaxic region of interest template. Clinic-radiological variables were analyzed by paired Student's t test. RESULTS: Ten migraineurs (4 men and 6 women) participated in the present study. Mean age was 54.1 (standard deviation [SD] 10.1) years. Mean duration of migraine was 25.3 (SD 9.8) years. Migraine subtype showed 4 MA and 6 MO patients. Mean score of HIT-6 was 66.3 (SD 11.7). Lomerizine treatment decreased HIT-6 scores significantly (P < .01). BP did not differ significantly after lomerizine treatment. Lomerizine treatment increased rCBF 20% approximately in the frontal, the parietal, the temporal, and the occipital region. CONCLUSIONS: The present study indicated a significant increase in interictal rCBF after lomerizine treatment in migraineurs. The upregulation of rCBF could contribute to the antimigraine mechanism of lomerizine.

Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis) with atypical encephalitis and painful testitis: a case report.

BACKGROUND: Kikuchi-Fujimoto disease is a self-limited clinicopathologic entity that is increasingly recognized worldwide. Kikuchi-Fujimoto disease is characterized by cervical lymphadenopathy occurring in young adults. Neurologic involvement is rare, and testitis directly caused by Kikuchi-Fujimoto disease has not yet been reported. CASE PRESENTATION: A 19-year-old man was brought to our clinic with complaints of fever, headache, fatigue, and left lower quadrant pain that had persisted for 3 weeks. On physical examination, painful cervical lymphadenopathies were observed. Meningitis was suspected based on a cerebrospinal fluid examination, and left-sided orchitis was diagnosed based on findings from magnetic resonance imaging and ultrasonography. However, neither antibiotics nor antiviral drugs were effective in treating the patient's symptoms. On the 20th day of hospitalization, the patient experienced a loss of consciousness, and brain T2-weighted magnetic resonance imaging showed asymmetrical, high-signal intensities in both basal nuclei and the left temporal lobe. Encephalitis was suspected, and the patient was treated with intravenous prednisolone pulse therapy (1 g/day) for 3 days and intravenous immunoglobulin therapy for 5 days. A left cervical lymph node biopsy showed apoptotic necrosis in paracortical and cortical areas with an abundance of macrophages and large lymphoid cells, which had irregular nuclei suggestive of Kikuchi-Fujimoto disease; the pathological findings from a brain biopsy were the same as those of the cervical lymph node biopsy. The encephalitis and cervical lymphadenopathies followed a benign course, as did the testitis. CONCLUSIONS: This is the first report of Kikuchi-Fujimoto disease involving painful testitis and pathologically proven asymmetrical brain regions. Kikuchi-Fujimoto disease should be included in the differential diagnosis when a patient presents with encephalitis, testitis, and fever of unknown origin.

Treatment with telmisartan, a long-acting angiotensin II receptor blocker, prevents migraine attacks in Japanese non-responders to lomerizine.

Lomerizine, calcium channel blocker, is the most used medication for migraine prophylaxis in Japan. The effectiveness of this drug is reported as 50-75%. Telmisartan is angiotensin II receptor blockers which plasma half-life is 24 h. We examined whether telmisartan has preventative benefits in lomerizine non-responsive migraineurs. Lomerizine non-responders received telmisartan (20 mg/day) for 3 months after the investigation period of 3 months. Blood pressure, frequency of headache days/month, headache severity, and doses of triptans and analgesics were analyzed by Wilcoxon signed rank test. Thirty-three migraineurs (25 women and 8 men) participated in this study. Seven patients had migraine with aura and 26 patients had migraine without aura. Mean age (SD) was 46.6 (10.3) years. Mean duration (SD) of migraine was 20.4 (12.5) years. Headache severity exhibited mild degree in 5 patients, moderate degree in 9 patients and severe degree in 19 patients. Mean frequency (SD) of headache days was 10.9 (8.5) days/month. Mean usage (SD) of triptans was 4.8 (5.1) tablets/month and that of analgesics was 15.2 (22.2) tablets/month. Five patients (15%) had hypertension. Telmisartan administration had benefits in 30 patients (90%). This medication significantly decreased frequency of headache days (P < 0.01) and headache severity (P < 0.01). Doses of triptans were reduced at one-third (P < 0.05) and those of analgesia at one-fifth after telmisartan treatment (P < 0.01). After telmisartan, mean (SD) of systolic blood pressure was significantly decreased (P < 0.05). The present study supported that telmisartan treatment had preventive effects in 90% of lomerizine non-responders. Telmisartan non-responders (10%) exhibited chronic migraine and long migraine duration.

Clinical Profile and Changes of Serum Lipid Levels in Epileptic Patients after Cerebral Infarction.

BACKGROUND: Antiepileptic drugs (AEDs) may increase development of dyslipidemia and cerebrovascular disease (CVD). We examined the clinical profile and changes of serum lipid levels after AED monotherapy in patients with poststroke epilepsy (PSE) after cerebral infarction (CI). SUBJECTS AND METHODS: Medical records were reviewed in consecutive 2144 CI patients. Monotherapy of valproate, carbamazepine (CBZ), phenytoin (PHT), zonisamide, levetiracetam, or lamotrigine was performed in PSE patients. Serum lipid levels were measured before and at 3 months after AED treatment. RESULTS: The prevalence of PSE was 7.0% in CI patients. The TOAST etiology disclosed large-artery atherosclerosis in 68 patients (45%), cardioembolism in 63 patients (42%), and undetermined cause in 19 patients (13%). CVD risk profile showed obesity of 18 patients (12%), current smoker of 30 patients (20%), hypertension of 75 patients (50%), diabetes mellitus of 32 patients (21%), dyslipidemia of 15 patients (10%), and atrial fibrillation of 63 patients (42%). CBZ or PHT administration increased serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels significantly compared to baseline and AED-untreated controls. Those levels were not increased significantly in other AED and control groups. Serum high-density lipoprotein-cholesterol and triglyceride levels did not differ statistically in all groups. CONCLUSIONS: The prevalence of post-CI epilepsy was 7.0%. The pathogenesis contributed to atherothrombosis and cardioembolism. CBZ or PHT administration increased serum TC and LDL-C significantly. Thus, we should pay more attention to serum lipid levels in patients receiving cytochrome P450 (CYP)-induced AEDs, and might considerer switching to non-CYP-induced AEDs in patients with unfavorable serum lipid changes.

Late-onset spinal form xanthomatosis without brain lesion: a case report.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive sterol storage disease caused by a mutated sterol 27-hydroxylase (CYP27A1) gene. Patients with typical CTX show neurological dysfunction including bilateral cataracts, paresis, cerebral ataxia, dementia, and psychiatric disorders, and magnetic resonance imaging (MRI) has revealed symmetrical lesions in the cerebellar white matter. CASE PRESENTATION: We report the case of a patient with late-onset spinal form CTX without brain lesion. He showed pyramidal tract signs, and impaired joint position and vibration sensation in the lower limbs. Cervical sagittal MRI demonstrated a longitudinally extensive white matter abnormality in the dorsal column of the C2-C7 spinal cord; however, a brain MRI revealed an absence of lesions, including in the cerebellar white matter. Genetic analysis of CYP27A1 revealed that the patient was compound heterozygous for p.Gln85Arg in exon 1, a novel mutation, and p.Arg405Gln in exon 7, a previously reported mutation. CONCLUSION: This is the first report of late-onset spinal form CTX without typical neurological symptoms, and the first report of p.Gln85Arg in CYP27A1. We speculate that spinal form CTX without brain lesion is a clinically and radiologically rare variation of CTX. Therefore, spinal xanthomatosis should be included in the differential diagnosis of chronic myelopathy even with late-onset and/or no other typical neurological findings.

An exploratory study of the efficacy and safety of yokukansan for neuropsychiatric symptoms in patients with Parkinson's disease.

The present study examined the efficacy and safety of yokukansan (YKS) in neuropsychiatric symptoms in patients with Parkinson's disease (PD) using the neuropsychiatric inventory (NPI). Twenty-five patients with PD (M:F 14:11; age 72 years) were enrolled and treated with YKS (7.5 g/day) for 12 weeks. The NPI was assessed at 0, 4, 8, 12 and 16 weeks. The patient's motor function and progression were evaluated using the Unified PD Rating Scale part III (UPDRS-III) and Hoehn and Yahr scale, respectively. The serum potassium concentration (sK) and all adverse events were recorded. The median NPI total score significantly decreased from 12 points at baseline to 4.0 points at 12 weeks (p = 0.00003). Within each NPI subscale, significant improvements were observed in hallucinations, anxiety and apathy. These symptoms tended to worsen after the completion of YKS treatment. Delusions, agitation, depression, euphoria, disinhibition, aberrant motor activity tended to improve but irritability showed no change. The median NPI subtotal scores, positive symptoms (delusions-hallucinations-irritability) significantly decreased (p = 0.01660) and negative symptoms (anxiety-apathy) significantly decreased (p = 0.00391). Both UPDRS-III and the Hoehn and Yahr scale showed no significant change. sK decreased mildly from 4.26 ± 0.30 to 4.08 ± 0.33 mEq/L. Two patients showed hypokalemia lower than 3.5 mEq/L without any corresponding symptoms; two patients showed listlessness and one patient showed drug eruption. Each recovered after discontinuation of YKS. YKS improved neuropsychiatric symptoms associated with PD, including hallucinations, anxiety and apathy without severe adverse events and worsening of Parkinsonism.

Open-label study to evaluate the pharmacodynamics, clinical efficacy, and safety of meropenem for adult bacterial meningitis in Japan.

The aim of this study was to assess the efficacy, safety, and concentration of meropenem in cerebrospinal fluid when meropenem (2 g every 8 h) was administered to Japanese adult patients with bacterial meningitis. Five Japanese patients (mean age 60.6 years [range 35-71]) were enrolled. Infection with Streptococcus pneumoniae (three patients), Streptococcus salivarius (one patient), and Staphylococcus aureus (one patient) was confirmed by cerebrospinal fluid culture. Meropenem (2 g every 8 h) was administered to all five patients. Treatment duration ranged from 14 to 28 days (mean 22.6 days). All the patients were successfully treated. The concentration of meropenem in cerebrospinal fluid ranged from 0.27 to 6.40 µg/ml up to 8.47 h and was over 1 µg/ml 3 h after starting meropenem infusion. In each patient, the present study confirmed for the first time that the concentration of meropenem in cerebrospinal fluid exceeded the minimal inhibitory concentration for these pathogens. Eleven clinical and laboratory adverse events considered to be related to meropenem were observed in all patients, but no serious adverse event and no discontinuance of treatment due to adverse events occurred. Thus meropenem appeared to be a well-tolerated and effective agent for Japanese adult patients with bacterial meningitis. 2 g every 8 h of meropenem was delivered to CSF and its concentration was exceed in MICs for the detected pathogens.

A case of sinus arrest and post-hiccup cough syncope in medullary infarction.

We describe asymptomatic sinus arrest and post-hiccup cough syncope in a patient with medullary infarction. A 78-year-old woman developed arrhythmia, hiccup, and cough syncope attacks. Neurological examination was not remarkable. Cough syncope occurs after hiccup attacks. Bradycardia and decreased blood pressure were also present after the beginning cough. Holter 24-hour electrocardiography monitor exhibited 65 episodes of asymptomatic sinus arrest more than 3 seconds. Magnetic resonance imaging disclosed acute infarction in the bilateral medial regions and the right tegmentum of the upper and middle medulla oblongata. Cerebral angiography showed severe atherosclerotic changes in the vertebral arteries. These clinicoradiological findings suggested that a distinct topography of medullary lesions could cause a series of cardiovascular and respiratory dysfunction. Thus, physicians should pay more attention to the medullary lesion in patients with arrhythmia and syncope.

Combined treatment of methylprednisolone pulse and memantine hydrochloride prompts recovery from neurological dysfunction and cerebral hypoperfusion in carbon monoxide poisoning: a case report.

A 49-year-old healthy man developed sudden unconsciousness under inadequate ventilation. Blood gas analysis showed carboxyhemoglobin of 7.3%. After normobaric oxygen therapy, he recovered completely 7 days later. At 3 weeks after carbon monoxide (CO) exposures, memory and gait disturbances appeared. Neurological examination revealed Mini-Mental State Examination (MMSE) score of 5 of 30 points, leg hyper-reflexia with Babinski signs, and Parkinsonism. Brain fluid-attenuated inversion recovery imaging disclosed symmetric hypointense lesions in the thalamus and the globus pallidus, and hyperintense lesions in the cerebral white matter. Brain single-photon emission tomography (SPECT) scanning with (99m)Technesium-ethyl cysteinate dimer displayed marked hypoperfusion in the cerebellum, the thalamus, the basal ganglia, and the entire cerebral cortex. He was diagnosed as CO poisoning and treated with hyperbaric oxygen therapy. The neurological deficits were not ameliorated. At 9 weeks after neurological onset, methylprednisolone (1000 mg/day, intravenous, 3 days) and memantine hydrochloride (20 mg/day, per os) were administered. Three days later, MMSE score was increased from 3 to 20 points. Neurological examination was normal 3 weeks later. Brain SPECT exhibited 20% increase of regional cerebral blood flows in the cerebellum, the thalamus, the basal ganglia, and the entire cerebral cortex. These clinicoradiological changes supported that the treatment with steroid pulse and memantine hydrochloride could prompt recovery from neurological dysfunction and cerebral hypoperfusion. Further clinical trials are warranted whether such combined therapy can attenuate neurological deficits and cerebral hypoperfusion in patients with CO poisoning.

A case of superficial hemisensory dysfunction due to operculo-insular infarction: radiological depiction of thalamocortical projections to the secondary somatosensory cortex.

A 64-year-old obese man developed hypesthesia in the left arm and leg. Neurological examination revealed decreased senses of pain, touch, and temperature in the left face, arm, trunk, and leg. Remaining functions were normal. Electrocardiogram showed atrial fibrillation. Somatosensory-evoked potentials using the stimulation in the median nerve were normal on both sides. Brain magnetic resonance imaging revealed acute infarction in the right parietal operculum and insula. There were no pathognomonic lesions in the postcentral gyrus, the thalamus, or the brain stem. Cardioembolic operculo-insular infarction was diagnosed. Diffusion tensor tractography map displayed the thalamocortical projections to the primary and the secondary somatosensory cortex (S2). These radiological findings supported that the operculo-insular lesion could disrupt the thalamo-S2 pathway. Thus, the thalamocortical disconnection between the thalamus to the S2 could cause superficial hemisensory dysfunction in the present patient.

Wegener granulomatosis-associated optic perineuritis.

UNLABELLED: INTRODUNCTION: We report two patients with optic perineuritis (OPN) and hypertrophic pachymeningitis in Wegener granulomatosis (WG). CASE REPORT: Patient 1: a 74-year-old man developed blurred vision in each eye, sequentially, over a year. In the first episode, visual acuity in the right eye was reduced to no light perception, and in the second episode, the vision in the left eye fell to 20/100. Brain and orbital magnetic resonance imaging (MRI) revealed abnormal enhancement in the meninges and the ipsilateral optic nerve sheath. T2-hyperintense lesions were found along the outer rim of the ipsilateral optic nerve. Seropositive proteinase-3-antineutrophil cytoplasmic antibody (PR3-ANCA), microhematuria and multiple pulmonary nodules suggested the diagnosis of WG. Steroid therapy was initiated 3 months after the first onset, but with no clinical response. At the 2nd episode, rapid administration of steroid ameliorated visual disturbance and MRI lesions markedly. Patient 2: a 72-year-old man developed blurred vision in each eye. Visual acuity measured no light perception in OD and 6/12 in OS. Gadolinium-enhanced MRI disclosed enhancement in the meninges and both optic nerve sheaths. T2-weighted imaging displayed hyperintense lesions along the outer rims of optic nerves. Otolaryngologic examination, seropositive PR3-ANCA and pulmonary nodules supported the diagnosis of WG. Steroid and cyclophosphamide treatment improved visual dysfunction and MRI lesions in the meninges and the optic nerve sheaths. COMMENT: The morphological similarity and the anatomical continuity between the meningeal and the perioptic tissues suggest that extension of granulomatous inflammation along such tissue planes accounted for visual loss in these two patients with WG.

Relationship between cervical cord 1H-magnetic resonance spectroscopy and clinoco-electromyographic profile in amyotrophic lateral sclerosis.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons, leading to limb paralysis and respiratory failure. METHODS: C1-C3 cord (1) H-magnetic resonance spectroscopy ((1) H-MRS) was performed in 19 patients with ALS and 20 controls. N-acetylaspartate (NAA), choline-containing compounds, creatine plus phosphocreatine (Cr), and myo-Inositol (m-Ins) were measured. ALS functional rating scale-revised (ALSFRS) and forced vital capacity (FVC) were assessed. The rates of decline were calculated at 6 months before and after (1) H-MRS. RESULTS: NAA/Cr and NAA/m-Ins were decreased significantly, and m-Ins/Cr was increased significantly in ALS patients compared with controls. NAA/Cr and NAA/m-Ins were correlated with ALSFRS and FVC and inversely linked to the decline rates. NAA/Cr, NAA/m-Ins, and m-Ins/Cr were altered markedly in 9 patients with denervation and neurogenic changes in both C2 paraspinal and upper limb muscles. CONCLUSIONS: These metabolite ratios were associated with disease progression and ongoing denervation in neck and hand muscles. C1-C3 cord (1) H-MRS might reflect anterior horn cell damage causing neck/arm weakness and respiratory dysfunction in ALS patients.

Limb-onset amyotrophic lateral sclerosis patients visiting orthopedist show a longer time-to-diagnosis since symptom onset.

BACKGROUND: There have been several reports concerning the survival time after symptom onset in patients with amyotrophic lateral sclerosis (ALS). However, little is known about how the choice of physician (i.e., general practitioner, neurologist, etc.) may affect the time it takes for a diagnosis of ALS to be made. METHODS: We conducted a retrospective study, covering a 20-year period, comparing the type of physician first consulted by an ALS patient at the time of initial symptoms and the amount of time that elapsed to the final diagnosis of ALS. A total of 202 patients were diagnosed and stratified according to the onset of ALS symptoms (bulbar onset [BO] and limb onset [LO]). We noted the type of physician first seen by the patient. The diagnostic interval was calculated as the time between onset of symptoms and the final diagnosis of ALS. RESULTS: A total of 202 ALS patients were examined. Clinical BO and LO was observed in 78 (36.6%) and in 124 (61.4%) of these patients, respectively. The type of physician examining these patients at the first symptoms of disease was as follows (BO and LO): neurologist (38.5% and 25.8%), general practitioner (14.1% and 35.5%), orthopedist (12.8% and 35.5%), otolaryngologist (15.4% and 0%), and neurosurgeon (14.1% and 3.2%). Mean diagnostic interval (standard deviation) for patients with either set of symptoms was 13.1 (6.5) months; the diagnostic interval of patients with BO and LO was 9.2 (4.5) and 15.2 (7.7) months, respectively. ALS diagnosis in LO patients was delayed by more than 10 months when the patient first consulted an orthopedist rather than a neurologist. CONCLUSION: More than 50% of the ALS patients included in this study did not visit a neurologist at the first symptoms of disease onset. The diagnosis of ALS was prolonged in LO patients visiting an orthopedist. We speculate that this increase in the diagnostic interval in LO patients visiting an orthopedist was due to a lack of bulbar symptoms in the early stages of this disease.

Clinicoradiological changes of brain NK/T cell lymphoma manifesting pure akinesia: a case report.

BACKGROUND: Pure akinesia (PA) is a distinct form of parkinsonism characterized by freezing phenomena. Little is known about brain tumor-associated PA. We highlight the clinicoradiological changes in a patient with PA and central nervous system (CNS) metastases of natural killer/T-cell lymphoma (NKTL). CASE PRESENTATION: A 68-year-old man with stage IVB extranodal NKTL developed a gait disturbance. Neurological examination of his gait revealed freezing, start hesitation, short step, forward flexion posture, festination and postural instability. Mild facial hypomimia and micrographia were observed. There was no rigidity or tremor in any of the four extremities. Brain magnetic resonance imaging (MRI) displayed T2-hyperintense lesions in the dorsal brainstem, cerebellum and periventricular white matter. Diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) revealed hyperintensity in these regions. Cerebrospinal fluid cytology revealed CD56-positive cells on immunohistochemical staining. The patient's neurological deficits did not respond to L-dopa treatment and intrathecal administration of methotrexate (MTX). Two weeks later, he displayed confusion and generalized convulsions. T2-hyperintense lesions spread to the basal ganglia and the infratentorial regions. Gadolinium enhancement was observed in the cerebellum and frontal subcortex. DWI and the ADC revealed diffusion-restricted lesions in the middle cerebellar peduncles, left internal capsules and cerebral white matter. MTX pulse therapy and intrathecal administration of cytosine arabinoside and MTX were performed. Two months later, his ambulatory state was normalized. Brain MRI also revealed marked alleviation of the infratentorial and supratentorial lesions. CONCLUSIONS: The clinicoradiological profile of our patient suggested that dorsal ponto-mesencephalic lesions could contribute to the pathogenesis of PA. Physicians should pay more attention to striking CNS seeding of metastatic NKTL. MTX pulse therapy had an excellent effect in improving serious symptoms and brain lesions in our patient.

Pulse wave velocity study in middle-aged migraineurs at low cardiovascular disease risk.

BACKGROUND: Migraine is associated with an increased risk for ischemic stroke and cardiovascular disease (CVD). Recent studies have suggested vascular dysfunction in the aorta, the brachial and femoral artery. Little is known about such arterial changes in Japanese midlife migraineurs. We aimed to evaluate arterial pulse wave velocity (PWV) and ankle-brachial index (ABI) in middle-aged migraineurs at low CVD risk. METHODS: Brachial-ankle PWV (baPWV) and ABI, using an oscillometric technique, were measured in 111 migraineurs (81 women and 30 men) and 110 controls. All participants had no CVD risk factors. Statistical comparison of baPWV and ABI between both groups and the relationship to clinical variables of migraineurs were analyzed. RESULTS: Twenty-two subjects had migraine with aura and 89 had migraine without aura. Mean age (SD) of migraineurs was 44.4 (8.4) years. Mean duration (SD) was 18.0 (10.8) years. Attack frequency was 60 subjects in ≥1 time/month and 51 subjects in <1 time/month. Mean score (SD) of Headache Impact Test-6 (HIT-6) was 61.4 (8.7). CVD risk profile did not differ statistically between migraineurs and controls. Mean baPWV (SD) of migraineurs was 1247 (189) cm/second in women and 1356 (126) in men. That of controls was 1138 (136) in women and 1250 (121) in men. baPWV was increased significantly in female and male migraineurs. Mean ABI (SD) was 1.05 (0.06; 1.04 [0.07] in men and 1.05 [0.06] in women) in migraineurs and 1.06 (0.07) in controls (1.05 [0.08] in men and 1.06 [0.08] in women). ABI did not differ statistically between migraineurs and controls. Migraine subtypes, duration, attack frequency, and HIT-6 score were not associated with baPWV and ABI. CONCLUSION: The present study indicated higher baPWV in midlife migraineurs without CVD risk factors. This pathogenesis could reflect distinct vascular reactivity rather than arterial stiffness due to atherosclerosis.

Cheiro-oral syndrome associated with lateral medullary infarction.

A 62-year-old man was admitted to our department because of the sudden onset of dysaesthesia in the right perioral region of the face and right hand. Neurological examination demonstrated a loss of pain and temperature sensation in both the right perioral region and in the fingers of the right hand. These findings suggested damage to parts of the ipsilateral spinothalamic and trigeminothalamic ascending tracts, producing restricted sensory impairment of the perioral region and ipsilateral hand. This is the first reported case of a medullary lesion causing cheiro-oral syndrome.

Serological profiles of urate, paraoxonase-1, ferritin and lipid in Parkinson's disease: changes linked to disease progression.

BACKGROUND: Oxidative stress plays a role in the pathogenesis of neuronal death. Serum levels of urate or lipid were associated with the incidence of Parkinson's disease (PD). OBJECTIVE: We compared urate, paraoxonase-1 (PON1), iron, ferritin and lipid in sera of 119 PD patients and 120 healthy controls matched by age, sex and body mass index. We aimed to elucidate whether those serological data are correlated with disease progression. RESULTS: Mean age (SD) of PD patients was 73.4 (8.7) years. Mean Yahr stage (SD) was 3.2 (0.9). Mean disease duration (SD) was 6.9 (5.1) years. Mean dose of L-DOPA (SD) was 355 (157) mg/day. As compared to controls, serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), urate and PON1 activity were significantly reduced, and serum ferritin levels were significantly increased in male and female PD patients. Serum urate levels and PON1 activities were inversely related, and serum ferritin levels were correlated with Yahr stage and PD duration in men and women. Serum levels of TC and LDL-C were inversely related to Yahr stage or PD duration in female patients. CONCLUSIONS: Our studies indicated serological profiles of urate, PON1, ferritin, TC and LDL-C in PD patients. These serological changes were linked to PD progression. Metabolism of lipid, oxidant- and antioxidant-related substances may contribute to the pathogenesis and the progression of PD.

Cardiovascular risk and neuroradiological profiles in asymptomatic vertebrobasilar dolichoectasia.

BACKGROUND: Clinicoradiological variability of vertebrobasilar dolichoectasia (VBD) is known. Little is known about cardiovascular disease (CVD) risk and neuroradiological profiles of asymptomatic VBD. METHODS: A total of 7,345 adults (5,534 men and 1,811 women) underwent physical checkup (PC) and brain magnetic resonance (MR) studies between 2004 and 2007. Asymptomatic VBD was diagnosed by neurological examination and MR angiography. Neuroradiological features were analyzed in VBD subjects. CVD risk factors were compared between VBD subjects and 5,000 controls matched by sex and age. RESULTS: Ninety-six subjects (85 men and 11 women) had asymptomatic VBD. The detection rate was 1.3% and the male/female ratio 2.5. The mean age +/- SD was 60.4 +/- 10.6 years (60.0 +/- 10.2 in men and 64.0 +/- 13.1 in women). As compared to controls, the frequency of hypertension, obesity, smoking, dyslipidemia, diabetes mellitus and a family history of stroke or CVD was increased significantly in VBD subjects. The mean diameter +/- SD of the basilar artery (BA) was 4.7 +/- 0.2 mm. Only 4 subjects (4%) had a severe degree of elongation and lateral displacement of the BA. Contact of the vertebral artery with the rostral ventrolateral medulla (AMC) was found in 81 subjects: right AMC in 22 subjects and left AMC in 59 subjects. Frequency of hypertension was significantly higher in the left-AMC subjects (57%) than in subjects with right AMC (9%) and no AMC (5%). Other neuroradiological findings revealed small infarcts in 42 subjects, brainstem compression in 4, hydrocephalus in 4 and brain saccular aneurysm in 3. CONCLUSIONS: Asymptomatic VBD was detected in 1.3% of the Japanese PC group. Our data indicated male predominance, multiple CVD risk factors, neurovascular hypertension and small infarcts in asymptomatic VBD.