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.

Alleviation of brain hypoperfusion after preventative treatment with lomerizine in an elderly migraineur with aura.

Previous studies of brain single-photon emission tomography (SPECT) showed changes of regional cerebral blood flow (rCBF) in migraineurs during prodromes or headache attacks. Little is known about how successful medication of migraine prevention can reflect rCBF in migraineurs. We highlighted alternation of brain SPECT findings in a migraineur with aura before and after prophylactic treatment with lomerizine, a calcium channel blocker. A 70-year-old man with migraine developed visual disturbance frequently at walking exercise for the recent 3 months. After this visual attack, a mild-degree of throbbing headache occured occasionally. Brain SPECT using (99m)Tc-ethyl cysteinate dimer was performed at interictal time of migraine. Brain SPECT before lomerizine treatment revealed hypoperfusion in the frontal, parietal, and occipital regions. He was diagnosed with recurrence of migraine with aura (MA). Lomerizine (10 mg/day, po) was administered for 3 months. MA and visual aura without headache were dramatically improved. Migraine attacks and visual disturbance were not induced at exercise. At 3 months after lomerizine medication, brain SPECT showed remarkable increase of rCBF. These SPECT changes of our patient indicated that antimigraine mechanism of lomerizine could contribute to restoration of cerebral hypoperfusion.

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.

A distinct phenotype of leg hyperreflexia in a Japanese family with Gerstmann-Sträussler-Scheinker syndrome (P102L).

Gerstmann-Sträussler-Scheinker Syndrome (GSS) is an inherited prion disease characterized by midlife onset and slowly progression of cerebellar ataxia and dementia. We report a distinct phenotype of leg hyperreflexia in a Japanese family with GSS. A 38-year-old woman noticed unsteady gait at 33 years of age. Afterwards, dysarthria and writing difficulty were appeared. Her family history revealed that her grandfather and her mother had a clinical history of unsteadiness and mental changes. At 1 year after clinical onset, neurological examination showed cerebellar ataxia and leg hyperreflexia. At 4 years after onset, she suddenly developed insomnia and nocturnal howling. Her mental status disclosed marked disorientation, anxiety and irritability. Muscle stretch reflexes were increased in four extremities with Babinski's signs. Remarkable dysarthria and cerebellar ataxia were presented. Brain diffusion weighted imaging showed extensive hyperintensity signal areas in the cerebral cortex. A point mutation of the prion protein gene (PRNP) at codon 102 resulting in the substitution of proline by leucine (P102L) was identified. PRNP polymorphism exhibited homozygous methionine at codon 129 and homozygous glutamate at codon 219. She had verbal perseveration, somnolence and myoclonus of lower limbs, leading to akinetic mutism at 4 months after neuropsychiatric events. Phenotypic hallmark of our patient indicates leg hyperreflexia from an early disease course. This neurological sign differs from the previously reported clinical expression of Japanese and foreign patients with GSS (P102L). Thus, physicians should pay more attention to phenotypic heterogeneity in this prion disease.

Neurosyphilis with unilateral optic tract lesion causing homonymous hemianopia.

INTRODUCTION: Homonymous hemianopia is not a rare symptom. Many causative lesions and pathologies are known, although a unilateral optic tract lesion caused by syphilis is rare. CASE REPORT: A 56-year-old woman developed a congruous right homonymous hemianopia and bilateral tonic pupils with irregular shape. Brain T2-weighted and fluid attenuated inversion recovery magnetic resonance imaging (MRI) revealed a spindle-like high-intensity lesion in her left postchiasmal optic tract. The rim of this lesion enhanced with gadolinium without meningeal enhancement. Serum and cerebrospinal fluid venereal disease research laboratory tests were positive. Cerebrospinal fluid contained 71 white blood cells/microL (mononuclear cells = 97%) and 48 mg/dL of protein. The hemianopia disappeared after administration of benzylpenicillin. CONCLUSIONS: Neurosyphilis should be added to the list of differential diagnoses for an isolated optic tract lesion.

A case of Vernet syndrome with varicella zoster virus infection.

A 40-year-old man was admitted to our department, because of sudden onset of dysphagia, hoarseness, left neck pain and headache. There were no skin lesions. On neurological examination, there were paralysis of the left soft palate and constrictor muscles of the pharynx, weakness of the left sternocleidomastoid and left upper trapezius. In cerebrospinal fluid (CSF) examination, cell count and protein concentration were elevated. Antibody titer to varicella zoster virus (VZV) was elevated in both the serum and CSF. And VZV-DNA was detected by PCR from CSF. Gd enhanced MRI showed the nodular lesion at the left jugular foramen. The diagnosis of Vernet's syndrome (VS) associated with VZV infection was made. The patient's symptoms were immediately improved with 30 mg of prednisone and 3 g of varaciclovir daily for 14 days. Only a few cases of VS due to VZV have been reported previously. Our case is the first case that detected VZV-DNA in CSF by PCR.

Cheiro-pedal syndrome following pontine infarction.

We report the case of a 64-year-old man with sudden onset of numbness in the right hand and foot. Neurological examinations were normal except for hypersthesia, and hyperalgesia of the right hand and foot. Brain MRI demonstrated a high signal intensity on T2-weighted image and a low signal intensity on T1-weighted image in the left tegmetum of the pons. He was diagnosed with pontine infarction presenting with cheiro-pedal syndrome (CPS). Damage in the sensory pathways can cause CPS. Difference in the threshold may explain the specific sensory pattern in this syndrome. Further examination of the relationship between sensory symptoms and localization on MRI is needed to clarify this syndrome.

T-588 protects motor neuron death following axotomy.

R(-)-1-(benzo [b] thiophen-5-yl)-2-[2-(N,N-diethylamino)ethoxy] ethanol hydrochloride) (T-588) enhances acetylcholine release. This compound slows the motor deterioration of wobbler mouse motor neuron disease and enhances neurite outgrowth and choline acetyltransferase activity in cultured rat spinal motor neurons. We examined the ability of T-588 on axotomized spinal motor neuron death in the rat spinal cord. After the postnatal unilateral section of sciatic nerve, there was approximately a 50% survival of motor neurons in the fourth lumbar segment. In comparison with vehicle, intraperitoneal injection of T-588 for 14 consecutive days rescued spinal motor neuron death. Our results showing in vivo neurotrophic activity of T-588 for motor neurons support the applicability of T-588 for the treatment of motor neuron diseases, such as amyotrophic lateral sclerosis and motor neuropathies.

T-588 protects motor neuron death against glutamate-induced neurotoxicity.

To examine the possible neuroprotective effect of T-588 against glutamate-induced neurotoxicity, we analyzed the pharmacological utility of T-588 in a postnatal organotypic culture model of motor neuron degeneration. Treatment with 10(-5) M of glutamate resulted a motor neuron loss and decreased activity of choline acetyltransferase (ChAT). Cotreatment of 10(-5) M of glutamate and T-588 revealed a protective effect against motor neuron death and decreased ChAT activity. We concluded that T-588 may play important roles in the survival and maintenance of spinal motor neurons in its neuroprotection against glutamate-induced neurotoxicity. Our data may provide a rationale for designing a therapeutic strategy for protection against pathologically induced motor neuron damage or cell death such as amyotrophic lateral sclerosis and motor neuropathy.

Temocapril prevents motor neuron damage and upregulation of cyclooxygenase-II in glutamate-induced neurotoxicity.

To examine the possible neuroprotective effect of temocapril, one kind of angiotensin-converting enzyme inhibitor, against glutamate-induced neurotoxicity, we analyzed the pharmacologic utility of temocapril in a post-natal organotypic culture model of motor neuron degeneration. Treatment with 10(-5) M of glutamate resulted in a motor neuron loss and decreased activity of choline acetyltransferase (ChAT). Cotreatment of 10(-5) M of glutamate and temocapril revealed protective effect on motor neuron death and decreased activity of ChAT. Next we performed reverse transcription-PCR analysis for cyclooxygenase-II (COX-II). COD-II mRNA was upregulated in glutamate-treated culture. Cotreatment with temocapril and glutamate inhibited upregulation of COX-II. Taken together, temocapril may have therapeutic potential for diseases which associate with upregulation of COX-II, in addition to its role in glutamate excitotoxicity.