Joe Aoyagi

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.

Limbic encephalitis associated with systemic lupus erythematosus

A 34-year-old woman with systemic lupus erythematosus (SLE) presented with general fatigue, seizures and memory loss. Magnetic resonance imaging of the brain showed a high signal area in the mesial temporal lobe bilaterally. Computed tomography scan of the chest and abdomen and ultrasound of pelvis detected no malignancy and tumour marker, antibodies to antineuronal antibodies (anti-Hu, anti-Ta and anti-Ma) and antibodies to voltage-gated potassium channels were all negative. The present case is limbic encephalitis (LE) associated with SLE and the pathogenesis may include autoimmunity shared. Our experience indicates that the immunologic spectrum of LE will expand to include additional immune mechanisms. Lupus (2009) 18, 1316—1319.

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 Vernets syndrome (VS) associated with VZV infection was made. The patients 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.

Depression in multiple sclerosis.

With interest we read the excellent article by Lobentanz et al. concerning a large number of multiple sclerosis (MS) patients in relation to disability, depressive mood and quality of life (QOL) (1). They reported MS patients had significantly lower QOL than healthy controls. Expanded disability states scale (EDSS) (2) and self-rating depressive scale (SDS) (3) predicted global QOL. They finally concluded that depressive mood is the main factor influencing QOL. Depression is common in MS patients and contributes to cognitive dysfunction. Diagnosing depression in MS patients and initiating appropriate treatment is important. We studied 48 patients with MS to elucidate the nature and frequency of the depressive state by comparing group of MS patients against ageand education-matched controls. We also examined the relationship between severity of the illness and the depressive state. Patients completed the SDS and underwent a complete neurological evaluation and were asked to rate their state of neurological well-being on a scale of 1 (poor) to 5 (normal). Neurological disability was measured using EDSS. Correlations between SDS score, self-rating scale and EDSS were performed. The mean SDS score was higher in the MS patients than those of the controls and there was no correlation between SDS score and EDSS. Furthermore, no relationship between SDS and duration of disease was observed. However, there was a correlation between SDS score and a self-rating assessment. A self-assessment rating scale may provide a valuable ascertaining of depression in MS patients. For psychological well-being it is important to MS patients that doctors should pay attention to mental care and medical treatment. In addition, improving the depression condition provides adequate treatment choice to MS patients. In our limited experience concerning the relationship between neurological disability and the depressive state in amyotrophic lateral sclerosis, upper motor neuron sign was correlated with depressive state (Y. Iwaski, unpublished data). Further studies are needed to clarify the relationship between neurological symptoms and signs, and the depressive state in MS patients.

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.

Cheiro-pedal syndrome following pontine infarction

Abstract 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.

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 99mTc-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.

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/&mgr;L (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.

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.

MG with distal muscle involvement.

Dear Sirs, We read with great interest the recent article by Werner et al. (1) concerning myasthenia gravis (MG) patients whose symptoms are primarily distal muscle involvement. They reported that six out of 84 MG patients showed a predominance of muscle weakness and fatiguability in the distal limb muscles. Furthermore, there was no difference between distal MG and MG with typical distribution of muscle weakness regarding age, gender and response to therapy. They also addressed diabetic neuropathy and myositis, and observed in one patient the associated disorder. To reach the diagnosis of MG, they applied the edrophonium chloride (Tensilon test), repetitive nerve stimulation and measurement of anti-acetylcholine receptor antibody (anti-Ach R ab). Distal muscle involvement is unusual in MG patients, and if neurologists examine these patients, many disorders may be ruled out. The article raised several questions. The first question raised is whether there is any difference for the diagnostic interval between typical and distal MG patients. Patients exhibiting distal muscle involvement does not necessarily lead to the diagnosis of MG. However, several differential disorders should be excluded as time may be needed to establish the correct diagnosis of MG. Tensilon test, repetitive nerve stimulations and anti-Ach R ab are not specific tests for diagnosing MG. One-third of the patients in the test were found to be negative for anti-Ach R ab. Was the anti-muscle-specific kinase (MuSK) antibody determined in seronegative MG cases (2)? Again distal muscle involvement in MG patients is unfamiliar to both neurologists and general physicians. What was the initial diagnosis of their six cases? It would be helpful for the authors to present the information concerning the value of creatine kinase and any reports of electromyographic findings. In their series concomitant disease, distal MG and myositis were seen. How did they diagnose these cases? Also, what is the possibility of myasthenic myopathy (3)? We have experienced several cases where clinical features were indicative of both MG and myositis, with a positive Tensilon test, elevation of anti-Ach R ab and creatine kinase. The difference between the ocular and limb muscle has been studied extensively (4), however little research has been done into the difference between proximal and distal muscles. Finally, we agree with their conclusion that distal MG is more frequent than generally assumed and should be considered in the differential diagnosis of disease with limb weakness.