摘要:Perivascular calcifications within the brain form in response to a variety of insults. While considered by many to be benign, these calcium phosphate deposits or “brain stones”can become large and are associated with neurological symptoms that range from seizures to parkinsonian symptoms. Here we hypothesize that the high concentrations of calcium in these deposits produce reversible, toxic effects on neurons that can be overcome with “bone”drugs that chelate solid phase calcium phosphates. We present preliminary findings that suggest a direct association between progressive neurological symptoms and brain calcification and the symptomatic improvement of seizures, headaches, and parkinsonian symptoms in patients treated with the bisphosphonate drug disodium etidronate, normally used to treat bone diseases. Future, longitudinal epidemiological studies and randomized trials will be needed to determine the true relationship between brain stones and neurological disorders as well as the utility of bisphosphonates in their prevention and treatment.
摘要:The occurrence of Creutzfeldt-Jakob disease (CJD) among American Indians and Alaska Natives in the United States was evaluated using national multiple cause-of-death data and medical information obtained from state health departments. Twelve CJD deaths were identified for 1981 through 2002, and the average annual age-adjusted death rate was 0.47 per million population. This rate was significantly lower than that for whites and similar to the rate for African Americans.
摘要:The authors report a Japanese patient with hereditary sensory and autonomic neuropathy type 2 (HSAN2) who has a new mutation of the HSN2 gene. The pathologic findings of the patient matched those of Canadian patients. They identified a homozygous 1134-1135 ins T mutation, resulting in a frameshift, and the subsequent premature stop codon at residue 378. These observations support the hypothesis that HSN2 is a causative gene for HSAN2.
摘要:Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of bile acid synthesis, caused by impaired hydroxylation of cholesterol side chains due to deficiency of the mitochondrial enzyme sterol 27-hydroxylase (CYP27A1), leading to accumulation of cholestanol and cholesterol in brain and other tissues. Elevated plasma cholestanol serves as a key marker for the clinical diagnosis of CTX. In the present report we describe a young man with CTX who was on high dose steroids for a misdiagnosed chronic inflammatory demyelinating polyneuropathy (CIDP) and had normal level of serum cholestanol. When steroids were discontinued, markedly elevated serum cholestanol was measured concomitant with marked clinical worsening. This observation may imply that steroids can lower plasma cholestanol, possibly by directly inducing residual CYP27A1 activity or by inducing alternative pathways for cholestanol elimination.
摘要:Thirty-six patients with subarachnoid and intraventricular cysticercosis were randomly assigned to receive albendazole at 15 or 30 mg/kg/day plus dexamethasone for 8 days. Results favored a higher dose, with larger cyst reduction on MRI at 90 and 180 days and higher albendazole sulfoxide levels in plasma. An albendazole course at 30 mg/kg/day combined with corticosteroids is safe and more effective than the usual dose. A single treatment was insufficient in intraventricular and giant cysts.
摘要:Patients with recurrent gliomas (n = 14) were treated with bevacizumab and carboplatin, cpt-11, or etoposide. Follow-up MRI scans were obtained 2 to 6 weeks after initiation of treatment. Contrast-enhancing tumor shrank in 7 patients, with reductions evident in as little as 2 weeks after initiation of therapy. Treatment seemed more effective for heterogeneously enhancing tumor compared with solidly enhancing tumor.
摘要:Arteriopathy of the central nervous system (CNS) complicated with ulcerative colitis is a rare condition, moreover the involvement of extracranial arteries has not been documented. An 18-year-old female complained of a severe pulsatile headache and nausea. She had been diagnosed and treated for ulcerative colitis for four years. Magnetic resonance imaging of the brain showed normal results; however, magnetic resonance angiography (MRA) revealed severe irregularity of the intracerebral arteries. After treatment with prednisolone, the patient fully recovered and the irregularity of the intracerebral arteries was dramatically improved. Vasculitis was strongly suggested as the cause of arteriopathy of the CNS in the present case. Involvement of extracranial arteries such as the carotid artery was also incidentally discovered by duplex ultrasonography and the HLA typing suggested genetic susceptibility to Takayasu’s arteritis. Findings from our patient suggest that extracranial arterial involvement should be considered in the case of arteriopathy of the CNS associated with ulcerative colitis.
摘要:The rate of brain atrophy and its relationship to clinical disease progression in progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is not clear. Twenty-four patients with PSP, 11 with MSA-P (Parkinsonian variant), 12 with Parkinson’s disease, and 18 healthy control subjects were recruited for serial MRI scans, clinical assessments and formal neuropsychological evaluations in order to measure brain atrophy during life and its association with disease progression in PSP and MSA-P. Serial scans were registered and rates of whole brain atrophy calculated from the brain-boundary shift integral. Regional rates of atrophy were calculated in the brainstem (midbrain and pons), the cerebellum, the lateral and third ventricles as well as frontal and posterior inferior brain regions, by locally registering to a region of interest in order to derive a local boundary shift integral (BSI). 82%of recruited subjects completed serial MRI scans (17 PSP, 9 MSA-P, 9 Parkinson’s disease patients and 18 healthy controls). Mean (SD) annualized rates of whole-brain atrophy were greatest in PSP: 1.2%(1.0%), three times that in controls. Mean (SD) midbrain atrophy rates in PSP, 2.2%(1.5%), were seven times greater than in healthy controls. In MSA-P, atrophy rates were greatest in the pons: 4.5%(3.2%), over 20 times that in controls and three times the rate of pontine atrophy in PSP. Atrophy rates in Parkinson’s disease were not significantly different from control rates of atrophy. Variability in the atrophy rates was lower when calculated using the BSI rather than manual measurements. Worsening motor deficit was associated with midbrain atrophy in PSP, and pontocerebellar atrophy in MSA-P. Worsening executive dysfunction was associated with increased rates of frontal atrophy in PSP. Cerebellar atrophy rates were better discriminators of MSA-P than cross-sectional volumes.We confirm that serial MRI can be applied to measure whole brain and regional atrophy rates in PSP and MSA-P. Regional rather than whole-brain atrophy rates better discriminate PSP and MSA-P from healthy controls. Clinico-radiological associations suggest these regional atrophy rates have potential as markers of disease progression in trials of novel therapies.
摘要:Treatment-related motor complications in Parkinson’s disease have been previously linked to disease-induced pre-synaptic alterations: dopaminergic denervation and changes in dopamine (DA) release patterns. The occurrence of such complications is also known to be partly dependent on the age of disease onset, occurring more frequently in patients with disease onset at a younger age. Using positron emission tomography (PET) and 4-h-long 18F-fluorodopa (FD) scans we have investigated in vivo an age dependence of disease-induced changes in DA turnover as a possible contributing factor to the agerelated differences in treatment-related motor complications. We evaluated the relative changes in DA turnover (measured by its direct inverse, effective DA distribution volume -EDV) and DA synthesis and vesicular storage capacity (quantified by the plasma input uptake rate constant Ki) in Parkinson’s disease patients as a function of age (n = 27, age range 38-79 years). After correcting for disease severity, a significant negative correlation was found between age and magnitude of disease-induced decrease in EDV and in Ki in the putamen (P < 0.001, P = 0.02, respectively). However, the difference between the disease-induced decrease in EDV and that in Ki also exhibited an age dependence (P < 0.001), indicating a relatively higher disease-induced increase in DA turnover (inverse of EDV) compared with the decrease in DA synthesis and storage rate in patients of younger age compared with older patients. This finding implies that DA turnover in younger-onset patients undergoes a relatively greater alteration and thus likely contributes to a greater imbalance between DA synthesis, storage and release, which could lead to larger swings in synaptic DA levels. It has indeed been suggested on theoretical grounds that such imbalance may contribute to the greater propensity for motor fluctuations. These results provide one possible explanation for the age-dependent occurrence of complications and support the existence of a pre-synaptic contribution to the occurrence of motor complications.
摘要:Experimental models of Parkinson’s disease have demonstrated abnormal synaptic plasticity in the corticostriatal system, possibly related to the development of levodopa-induced dyskinesias (LID). We tested the hypothesis that LID in Parkinson’s disease is associated with aberrant plasticity in the human motor cortex (M1). We employed the paired associative stimulation (PAS) protocol, an experimental intervention involving transcranial magnetic stimulation (TMS) and median nerve stimulation capable of producing long-term potentiation (LTP)-like changes in the sensorimotor system in humans. We studied the more affected side of 16 moderately affected patients with Parkinson’s disease (9 dyskinetic, 7 non-dyskinetic) and the dominant side of 9 age-matched healthy controls. Motorevoked potential (MEP) amplitudes and cortical silent period (CSP) duration were measured at baseline before PAS and for up to 60 min (T0, T30 and T60) after PAS in abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. PAS significantly increased MEP size in controls (+74.8%of baseline at T30) but not in patients off medication (T30: +0.07%of baseline in the non-dyskinetic, +27%in the dyskinetic group). Levodopa restored the potentiation of MEP amplitudes by PAS in the non-dyskinetic group (T30: +64.9%of baseline MEP)-but not in the dyskinetic group (T30: -9.2%of baseline). PAS prolonged CSP duration in controls. There was a trend towards prolongation of CSP in the non-dyskinetic group off medications but not in the dyskinetic group. Levodopa did not restore CSP prolongation by PAS in the dyskinetic group. Our findings suggest that LTP-like plasticity is deficient in Parkinson’s disease off medications and is restored by levodopa in nondyskinetic but not in dyskinetic patients. Abnormal synaptic plasticity in the motor cortex may play a role in the development of LID.
摘要:Objective. -To compare the clinical characteristics of familial hemiplegic migraine (FHM), sporadic hemiplegic migraine (SHM), and nonhemiplegic migraine with aura (NHMA) and further, to compare subtypes of NHMA. Background. -To discover distinct underlying genetic and pathophysiological mechanisms it is crucial to drive clinical subdivision of migraine with aura as far as possible. The documentation of subtypes of migraine with aura depends on the clinical characteristics as the genetic mechanisms are unknown except for the dominantly inherited FHM. Methods. -Patients with FHM, SHM, or familial NHMA were recruited from specialist practice and diagnosed according to the International Classification of Headache Disorders (ICHD) in a validated interview by a physician. Patients with hemiplegic migraine had a physical and neurological examination. Patients with population-based NHMA from a previous Danish study were used for comparison. Results. -We recruited 147 patients with FHM, 105 with SHM, and 362 with familial NHMA. FHM and SHM had similar aura and headache characteristics. Patients with FHM and SHM were more likely to experience two or more aura symptoms (100%vs. 31%, P < .0001), they more often had prolonged aura symptoms, they almost always had a headache associated with the aura (93%vs. 58%, P < .0001), and they more frequently had basilar-type symptoms (69%vs. 10%, P < .0001) than patients with population-based NHMA. Patients with familial NHMA were more likely to experience two or more aura symptoms than patients with population-based NHMA (61%vs. 32%, P < .0001). Within the subtypes of NHMA, patients with typical aura with migraine headache had an earlier age at onset (20 ±10 vs. 23 ±13 years, P = .044) and a higher co-occurrence of migraine without aura (43%vs. 22%, P= .002) than patients with typical aura with nonmigraine headache. Conclusions. -The present study proves that distinct subtypes of migraine with aura exist. It further underlines the phenotypic differences between the different subtypes of migraine with aura which likely are caused by different etiological mechanisms. In future studies FHM, SHM, and NHMA therefore should be analyzed as separate entities and patients with NHMA may be stratified by ICHD-2 subtype of NHMA.
摘要:Fibromyalgia syndrome (FMS) is a chronic pain syndrome of unknown aetiology characterized by diffuse pain over more than 3 months and tenderness in specific sites named tender points. The aim of this study was to assess the prevalence and severity of FMS among patients suffering from episodic migraine. Ninety-two consecutive patients (20 male, 72 female) fulfilling the International Headache Society criteria for migraine with and without aura from a tertiary headache clinic were evaluated. A headache and generalized pain history was recorded, tender points were evaluated by thumb palpation. The diagnosis of FMS was made based on the 1990 American College of Rheumatology classification criteria for FMS. Sixteen (22.2%) of the female patients and none of the male patients were diagnosed as suffering from FMS. Migraine severity and characteristics were similar to other female migraine patients. Patients suffering from migraine-FMS had lower quality of life scores and higher levels of mental distress. A high incidence of FMS was found among female migraine patients but not in males. The coexistence of FMS should be considered when choosing a prophylactic migraine therapy.
摘要:Axon-derived neuregulins (NRGs) are a family of growth factors whose binding to ErbB tyrosine kinase receptors promotes the maturation, proliferation and survival of Schwann cells (SCs). Correct NRG/ ErbB signaling is essential for the homeostasis of axonal-glial complexes and seems to play a role in peripheral nerve repair. The potential involvement of ErbB receptors in human peripheral neuropathies has not been clarified. Therefore, we assessed the immunoreactivity for EGFR(ErbB1), ErbB2, and ErbB3 in nerve biopsies from patients with different for ms of Charcot-Marie-Tooth disease, type 1, (CMT1), as compared to others with inflammatory neuropathies and controls. The most notable changes consisted in th e overexpression of ErbB2 and ErbB3 by SCs of nerves from CMT1A patients. These findings are consistent with an impairment of SC differentiation and expand the molecular phenotype of CMT1 A. The upregulation of these receptors may play a ro le in the inhibition of myelination or in the promotion of recurrent demyelinati on and axonal damage.
摘要:Objective. -To retrospectively examine the reported history of and the disability caused by headaches in patients presenting for evaluation and treatment of orofacial pain. Background. -More than 81%of patients with the chief complaint of pain in the orofacial region concomitantly report pain in other body locations. Among the comorbidities frequently reported with orofacial pain are a variety of different headaches types, including migraines, tension type headaches, and chronic daily headaches. The extent of the disability caused by those headache complaints in a large patient population is unknown. Methods. -The Migraine Disability Assessment (MIDAS) is administered to all patients as a part of the initial assessment at the Orofacial Pain Center. This investigation is retrospectively examined the reported history of and the disability caused by headaches in patients who presented for evaluation and treatment of orofacial pain in the Orofacial Pain Center, National Naval Medical Center, Bethesda, MD, between the dates of 1 September 2003 and 1 December 2004. Results. -In the present study 261 (61.3%) patients reported a headache complaint and 100 (38%) fulfilled the criteria for migraine with or without aura. MIDAS scores were reported by 55.3%of 426 patients with the mean score of 23.68. There were no significant differences in MIDAS scores in relation to the presence or absence of an intracapsular disorder. Patients with masticatory and/or cervical myalgia demonstrated significantly higher MIDAS scores when compared to patients without myalgia. Conclusions. -These findings clearly demonstrate the necessity for evaluation of headache and related disability in orofacial pain patients.
摘要:The particular mechanisms of migraine anticipation by different precipitating agents are still unknown. The contingent negative variation (CNV) was recorded in the premenstrual and ovulation phases of the cycle in both rest and stress conditions in 17 migraine and 15 healthy women. In migraineurs a significant increase of amplitude of the initial CNV component in the premenstrual phase compared with ovulation was observed. During both the ovulation and premenstrual phases both migraineurs and controls demonstrated a significant increase of the CNV amplitude on stress. The increase of the amplitude on stress in the premenstrual phase was more pronounced in migraineurs. This study shows that stress and menstrual cycle are associated with changes of the initial CNV amplitude, probably indicating a higher probability of migraine attacks.
摘要:We report three patients with a syndrome that fulfilled clinical and laboratory criteria for definite chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who failed immunosuppressive treatment and eventually developed progressive amyotrophic lateral sclerosis (ALS). Mean disease duration was 23 months (13-38) before death. Two patients had a family history of ALS without mutations of the SOD1 gene. Postmortem examination in one patient showed an endoneurial infiltration of mononuclear cells in lumbar roots and distal and proximal peripheral nerves, mainly around myelinated fibers, with demyelination and axonal loss, consistent with CIDP. The spinal cord revealed severe neuronal loss in the anterior horn, axonal loss in the corticospinal tract, and large numbers of phagocytes in the anterior and lateral tracts, indicative of ALS. Whether demyelinati ng polyneuropathy was coincident with ALS or was a cause or consequence of motor neuron degeneration in these patients remains to be elucidated. This unusual co mbination may provide an important clue in elucidating the pathogenesis of ALS i n some patients.
摘要:Six migraine patients experienced significant topiramate-related cognitive and language dysfunction that improved with donepezil treatment and allowed uninterrupted topiramate use. These patients represent the first report of topiramate-related cognitive and language dysfunction that improved with a cholinesterase inhibitor. Although, the mechanism responsible for this effect is uncertain, cholinesterase inhibition resulting in cholinergic augmentation and enhanced cognition probably account for some if not most of the improvement.
摘要:Lysosome-associated membrane protein-2 deficiency (LAMP2 deficiency), or Danon disease, is a rare X-linked lysosomal disease characterized by cardiomyopathy, vacuolar myopathy, and mental retardation. Less than 20 families with mutations of the Lamp-2 gene have been reported. We describe a family from Sardinia with eight affected patients (4 females and 4 males) and a novel mutation in exon 2 of the Lamp-2 gene (c.102103delAG). Females developed isolated cardiomyopathy in adulthood, whereas males presented with cardiomyopathy, myopathy, and mental retardation before the age of 20 years. Cardiomyopathy was lethal in three females in their 40s and in three males before the age 20 years. One patient was su ccessfully treated by heart transplantation with more than 5-year follow-up. T his study demonstrates that Danon disease is a frequently fatal condition that i s potentially treatable with heart transplantation.
摘要:The authors retrospectively reviewed all neurologic records of an emergency unit from 1999 to 2003 to identify a potential association between lunar phases and seizure occurrence. Overall 859 patients admitted for seizure occurrence were divided into the four quarters of the synodic month according to moon phases. A significant clustering of seizures around the full moon period was observed, supporting the ancient belief of periodic increased seizure frequency during full-moon days.
摘要:The presence of an orbital bruit in a patient with daily headache suggests an underlying secondary cause. A case is presented in which a unilateral orbital bruit appeared to be the only physical sign of a dural venous sinus thrombosis.
摘要:The criteria for chronic migraine (CM), as proposed by the Second Edition of the International Classification of Headache Disorders (ICHD-2) is very restrictive, excluding most patients that evolve from episodic migraine. In this study we empirically tested three recent proposals for revised criteria for CM. We included individuals with transformed migraine (TM) with or without medication overuse, according to the criteria proposed by Silberstein and Lipton. All individuals had headache calendars for at least three consecutive months. We assessed the proportion of subjects that fulfilled ICHD-2 criteria for CM or probable chronic migraine with probable medication overuse (CM+). We also tested three proposals for making the CM criteria more inclusive. In proposal 1, CM/CM +would require at least 15 days of migraine or probable migraine per month. Proposal 2 suggests that CM/CM +would be classified in those with ≥15 days of headache per month, where at least 50%of these days are migraine or probable migraine. Proposal 3 suggests that CM/CM +would be classified in those with chronic daily headache and at least 8 days of migraine or probable migraine per month. Among TM sufferers, 399 (62.5%) had TM with medication overuse, and just 10.2%were classified as CM+158 (37.5%) had TM without medication overuse; just nine (5.6%) met current ICHD-2 criteria for CM. Using the alternative criteria, proposal 1 included 48.7%of patients with TM without medication overuse; proposal 2 captured 88%, and proposal 3 classified 94.9%of these patients. For TM with medication overuse, the proportions for proposals 1-3 were, respectively, 37%, 81%and 91%. The differences were statistically significant, favouring proposal 3. Consistently, criteria for CM and CM+should be revised to require at least 8 days of migraine or probable migraine per month, in individuals with 15 or more days of headache per month.
摘要:Pure neural leprosy (PNL) is often difficult to diagnose when acid-fast bacilli (AFB) cannot be detected. We undertook the present study to evaluate use of the polymerase chain reaction (PCR) in diagnosing PNL. Fifty-eight patients (41 men and 17 women) suspected of pure neural leprosy (PNL) were examined. Patients were classified as borderline tuberculoid (BT, 40 cases) and polar tuberculoid (TT, 18 cases) types. Nerve biopsy was performed and was positive for AFB in 20 patients (all BT patients), i.e., 34.5%of total cases. DNA was extracted from the nerve biopsy samples and amplified using PCR for a specific repeated sequence of DNA from Mycobacterium leprae. PCR analysis was positive in the nerve samples from 29 patients (50%), 27 of the BT type, and 2 of the TT type patients. Further, PCR analysis was positive in 14 of 38 cases that were negative for AFB by nerve biopsy, of which 12 were of the BT type and 2 the TT type. PCR analysis proved to be a useful method to investigate pure neural leprosy, enabling confir mation of the diagnosis in more than a third of the cases that were negative for AFB by nerve biopsy.
摘要:The authors examined blood pressure, glucose, insulin, and neurotensin before and after intake of 75 g glucose with or without voglibose in 28 neurologic patients and 20 healthy controls. Voglibose significantly prevented hypotension and neurotensin increment after glucose intake and had no influence on glucose or insulin increment. These results suggest that voglibose benefits postprandial hypotension.
摘要:A 44-year-old woman developed a severe right frontotemporal headache, retro-orbital pain, and, later, diplopia owing to right sixth nerve palsy. The brain MRI demonstrated strong enhancement of the right cavernous sinus. The sixth nerve palsy and headache improved with steroid therapy after 6 weeks. At that time, she suffered right peripheral facial nerve palsy. Enhancement of the distal canalicular and labyrinthic segment of the right facial nerve was found on contrast-enhanced MRI. To our knowledge, this is a very rare case of Tolosa-Hunt syndrome with facial nerve palsy, with simultaneous enhancement of the cavernous sinus and facial nerve on contrast-enhanced MRI.
摘要:We describe a 48-year-old woman with seronegative myasthenia gravis (MG) and high-titer of anti-MuSK antibody. She had severe bulbar and respiratory weakn ess with minimal limb weakness for 2 years. Her disease responded poorly to all the conventional immunosuppressive regimens. Treatment with immunoablative dose of cyclophosphamide led to dramatic and sustained remission of her symptoms. Hig h-dose cyclophosphamide is an effective alternative in patients with unusually refractory disease.
摘要:One aim of the Vg study of headache epidemiology was to depict the total panorama of headaches in a small-sized, Norwegian community at the end of the 20th century. In the present part of the study, a search was made for the rare, global headaches. Various, relatively unknown headache categories were observed, such as hydrogen sulphide intoxication (n = 2)-after exposure to H2S ambient air concentrations of ≥100 p.p.m. In Vg, nitroglycerine headache (‘dynamite headache‘) proved to be a relatively frequent disorder (n = 13). This represents approximately 0.7%of the study group. A main reason for this, in all probability unusually high frequency is that there previously have been soapstone mines within the precincts of the parish. Another relatively frequently occurring headache followed exposure to wind (n = 7; 0.38%). Ice-cream headache was rare (n = 3; 0.16%), when only the general question was asked: ‘other headaches?’. Approximately 7 years later, an ad hoc procedure was adopted: 50 parishioners who did not answer positively concerning ice-cream headache on the first examination were asked specific questions concerning ice-cream headache. Four had had such an experience, i.e. prevalence of 8%, which is 50 times higher than the original result, but still a rather low prevalence when compared with the mean prevalence from other studies: 39%. This demonstrates that the result as regards prevalence, even for a headache such as ice-cream headache, to a large degree depends upon the interview technique used.