Woman with acute onset involuntary limb movements.

CLINICAL INTRODUCTION: An 88-year-old woman presented with acute onset of involuntary limb movements for one day. Two days prior she had fallen a suffered a left hip contusion but no head trauma. There was no fever or difficulty breathing. Her heart rate was 72 bpm with blood pressure of 109/68 mm Hg. Physical examination revealed restricted left hip motion due to pain and a sustained twisted posture of the upper extremity without paresis. Glasgow Coma Scale was 15, and there was no evidence of Kernig's or Brudzinski's sign. She underwent a hip X-ray and non-contrast CT scan (figures 1 and 2).emermed;36/7/415/F1F1F1Figure 1Anteroposterior X-radiograph of the hip.emermed;36/7/415/F2F2F2Figure 2A non-contrast brain CT. QUESTION: What is the most likely cause of the clinical presentation?Acute meningitisCerebral fat embolismHaemorrhagic strokeHypertensive encephalopathy For answer see page 2 For question see page 1.

Analysis of trunk rolling in Parkinson's disease patients using a mattress mobility detection system.

BACKGROUND AND OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative condition characterized by motor dysfunction and various types of non-motor impairments. The reaction time and movement time are reported to become more severe delayed in worse PD patients. Most tools for evaluating motor impairment are limited by relying on subjective observations and being qualitative in design. The aim of this study was to investigate trunk rolling performance in PD patients by using a recently developed system to detect turning in bed. METHODS: The study included 20 PD patients and 42 healthy controls. A mattress mobility detection system was employed for quantitative measurements. Each test session consisted of subjects starting by lying in a supine position on a bed and rolling 10 times onto their left side and 10 times onto their right side. Strain gauges mounted under the feet of the bed recorded changes in the center of pressure (CoP). RESULTS: For turning back, the patients compared with the controls had significantly longer movement time (P = 0.017), longer time to peak counteraction (P = 0.001), larger ratio of peak counteraction to movement time (P = 0.006), shorter CoP displacement (P < 0.0001), slower turning speed (P = 0.000), weaker peak counteraction (P = 0.013), and smaller ratio of peak counteraction to weight (P = 0.032). Results for turning over were similar except there was no significant difference in the ratio of peak counteraction to weight. CONCLUSIONS: The mattress mobility detection system was useful for objectively assessing trunk rolling performance of PD patients. Improved assessment of trunk function in PD patients could lead to better treatments and improved rehabilitation procedures.

Acute Onset of Parkinsonism an End-Stage Renal Disease Patient.

PURPOSE: The osmotic demyelination syndrome (ODS) has been identified as a neurological complication of the rapid correction of hyponatremia. In recent years, however, various medical conditions have been associated with the development of ODS, irrelevant to changes in serum sodium. We present a rare case of a eunatremic patient who developed ODS with manifestation of parkinsonism. CASE: A 55 years old woman who has hypertension, type 2 diabetes nephropathy in end-stage renal disease under maintenance hemodialysis came to us with complaint about newly developed resting tremor of bilateral upper limbs, slowness of movements and small shuffling steps. Brain magnetic resonance imaging (MRI) showed bilateral lentiform nuclei demyelination. ODS was diagnosed concerning the comorbidities and her medical history. Her neurological deficits improved dramatically after treatment of Ropinirole. CONCLUSION: ODS may develop in patient with risk factors regardless of change in serum sodium concentration. Brain MRI could help in early detection of the demyelination. Secondary parkinsonism may occur as a rare manifestation of ODS. Supportive treatment, monitoring of vital signs and neurological deficits are warranted. Dopaminergic agent may be beneficial in symptomatic control.

Posterior Reversible Encephalopathy Syndrome Mimicking Brainstem Infarction: A Dilemma.

PURPOSE: We had recently reported one case at American Journal of Emergency Medicine about centralvariant posterior reversible encephalopathy syndrome (PRES) in an 84-year-old woman with an initial misdiagnosis as central pontine myelinolysis (CPM). Here, we introduce another case of centralvariant PRES in a 49-year-old man mimicking as acute brainstem infarction in the cranial computed tomography (CT) findings. CASE REPORT: A 49-year-old man was admitted to the emergency department with a 5-day history of vertigo, cognitive decline, and difficulty in walking. Neurologic examination revealed drowsiness with a Glasgow Coma Scale score of 12 (eye opening: 3, best verbal response: 4, and best motor response: 5), slow movement in pursuit and saccades, and gait instability with a Medical Research Council scale of grade 4-5. Non-contrast cranial CT showed hypodense lesions in the pons, and antiplatelet agent was initiated for presumed pons infarction. However, the brain magnetic resonance imaging (MRI) demonstrated vasogenic edema in the corresponding area, consistent with the diagnosis of central-variant PRES. CONCLUSION: This case report raises the awareness that when hypodense brainstem lesions on brain CT in patients with progressive neurological dysfunction, the rare condition of central-variant PRES should be considered in the differential diagnosis to avoid inadequate management. Cranial magnetic resonance imaging (MRI) may help in diagnosis and dealing with of these patients with similar radiological and clinical abnormalities.

Risk Factor Stratification for Intracranial Stenosis in Taiwanese Patients With Cervicocerebral Stenosis.

BACKGROUND: Intracranial stenosis (ICS) is a major determinant of ischemic stroke in Asians. We determined the clinical significance of different risk factors and the role of ICS in Taiwanese patients with varied distributions of cervicocerebral stenosis. METHODS AND RESULTS: Presence of extracranial carotid stenosis (ECS, ≥70%) and ICS (>50%) was examined in 13 539 patients using ultrasonography and magnetic resonance angiography, respectively. Seven hundred thirty-three patients with non-ECS/ICS (n=372), isolated ICS (n=112), isolated ECS (n=121), or combined ECS/ICS (CEIS, n=128) were selected. Prevalence of ischemic stroke in each group was compared, and risk factors for stenosis were determined. The area under the receiver operating characteristic curve for each risk factor was calculated. Prevalence of ischemic stroke was highest in patients with CEIS (odds ratio 15.86; P<0.001), followed in decreasing order by those with isolated ICS (odds ratio 7.16; P<0.001), isolated ECS (odds ratio 1.77; P=0.011), and non-ECS/ICS. Multivariate logistic regression analysis revealed that hypertension, coronary artery disease, and smoking were risk factors for isolated ECS; hypertension, diabetes mellitus, coronary artery disease, and smoking were risk factors for isolated ICS; and diabetes mellitus, coronary artery disease, and smoking were risk factors for CEIS. Smoking, diabetes mellitus, and coronary artery disease were the greatest contributors to CEIS, isolated ICS, and isolated ECS, respectively. CONCLUSIONS: CEIS was associated with higher odds of ischemic stroke compared with isolated ICS and isolated ECS. Smoking and diabetes mellitus, major determinants of CEIS and isolated ICS, should be targeted in therapeutic strategies to reduce the risk of ischemic stroke.

Post-insult valproate treatment potentially improved functional recovery in patients with acute middle cerebral artery infarction.

Animal stroke models suggest that valproate has multiple neuroprotective mechanisms against ischemic brain damage. This study investigated whether valproate improves functional recovery in patients with acute middle cerebral artery (MCA) infarction. This was an open-label controlled trial. Three to 24 hours after acute MCA infarction, patients were assigned to either the valproate group (n = 17) or the non-valproate group (n = 17). The valproate group received intravenous valproate (400 mg) at enrollment, and then every 12 hours for three days, followed by oral valproate (500 mg) every 12 hours for three months. Neurological function, laboratory data, and brain magnetic resonance imaging were examined at stroke onset, and at two-week and three-month follow-up. No significant differences were observed between the groups with regard to demographics or baseline characteristics. All patients were elderly, had a high pretreatment score on the NIH stroke scale (NIHSS), and slow stroke lesion growth with a final large infarct volume at two-week follow-up. At the three-month follow-up, functional outcome between pre- and post-treatment had improved significantly in the valproate group (NIHSS, p = 0.004; modified Rankin scale (mRS), p = 0.007; Barthel index (BI), p = 0.001). No such improvement was noted in the NIHSS or mRS for the non-valproate group, though mild improvement was seen on the BI (p = 0.022). This open-label trial is the first to demonstrate that valproate treatment markedly improves functional outcome in patients with acute MCA infarction.

Homocysteine induces cerebral endothelial cell death by activating the acid sphingomyelinase ceramide pathway.

Homocysteine (Hcy) levels may rise after a stroke, but the mechanism of Hcy-induced cerebral endothelial cell (CEC) dysfunction has not been explored. In this study we examined the role of the acid sphingomyelinase (Asm)-ceramide pathway in the molecular mechanism of Hcy-induced CEC dysfunction. Murine CECs were prepared from fresh mouse brains. CECs were treated with 50-500 µM Hcy and 30-100 µM C2-ceramide for 48 h. Sphingomyelinase assays were performed to determine Asm activity. Quantitative assessments of cell survival and death by the MTT reduction and LDH release were conducted. Treatment of murine CECs with Hcy and ceramide caused cell death in a dose-dependent manner as determined by LDH and MTT assays. 250 µM Hcy and 50 µM C2-ceramide caused 50% cell death. Hcy induced murine CEC death also occurred in a time-dependant manner with substantial cell death noted as early as 24h after Hcy exposure. C2-ceramide-induced murine CEC death occurred earlier than Hcy-induced cell death by about 18h. Hcy treatment increased Asm activity and intracellular ceramide accumulation. This study demonstrated that Hcy and C2-ceramide can cause murine CEC death. Hcy induces CEC death possibly by activating the Asm-ceramide pathway.

[Tremor].

Tremor is the most common involuntary movement disorder. It can be an isolated symptom or a symptom of another neurological disorder, such as dystonia, Parkinson disease, spinocerebellar ataxia et al. It is an unintentional, somewhat rhythmic, muscle movement involving to-and-fro movements of one or more parts of the body. It can affect the hands, arms, head, vocal cord, jaw, chin, and legs. Most tremors occur in the hands. Clinically, the most useful way to categorized tremor is whether it occurs mainly at rest, on postural, or during movement (kinetic tremor). Tremor is most common classified by different clinical features and cause or origin; include essential tremor, Parkinsonian tremor, cerebellar tremor, dystonic tremor, orthostatic tremor, physiologic tremor, and psychogenic tremor. Diagnosis need a detail history (include familial inheritance, drugs exposure, alcohol consumption or withdraw); complete physical examination and laboratory tests. Electromyography is also a simple and quick method with which to calculate tremor frequency and amplitude for assisting diagnosis. Treatment for majority of tremor syndrome is purely symptomatic, and is similar regardless of the underlying cause of the tremor. There are different medicines to try in order propranolol, clonazepam, primidome and gabapentin for limb tremors, or trihexyphenidyl for dystonic tremor. Focal botulinum toxin injection may be help in focal tremor. Neurosurgery is only indicated in severe tremor, such as deep brain stimulation (DBS) of subthalamic nucleus for primary or secondary parkinsonian tremor.

(99m)Tc-TRODAT-1 SPECT study in evaluation of Holmes tremor after thalamic hemorrhage.

Holmes tremor is also known as rubral or midbrain tremor. The tremor usually involves lesions near the red nucleus and the nerve fiber tracts originating in the cerebellum and the substantia nigra. We report a case of a 62-year-old woman who presented with Holmes tremor 5 months after a left thalamic hemorrhage, with a partial recovery 3 years later. Sequential technetium-(99m)TRODAT-1 single-photon emission computed tomography (SPECT) of the patient's brain revealed partially improved tracer uptake reduction in the striatums, particularly on the left side. We propose that involvement of both the nigrostriatal and the dentate-rubro-thalamic pathways are essential in the pathogenesis of Holmes tremor after a thalamic lesion, and regeneration of the nigrostriatal system is possible in this type of tremor after the initial degeneration. The (99m)Tc-TRODAT-1 SPECT study is a useful and convenient tool for evaluating the nigrostriatal dopamine function in patients with Holmes tremor.

Spinal myoclonus in subacute combined degeneration caused by nitrous oxide intoxication.

A 26-year-old patient developed ascending weakness and paresthesias. Megaloblastic anemia and mildly reduced serum vitamin B12 (B12) concentration were noted. Myoclonus-like muscular contractions appeared over four extremities and in the trunk. She admitted inhaling nitrous oxide (N2O) as a euphoriant repeatedly at party. Following parenteral B12 administration, her neurological deficit promptly resolved. This case demonstrated the abuse of N2OI is an important cause of subacute combined degeneration (SCD) of the spinal cord. To our knowledge, this is the first report of involuntary movements in a patient with N2O intoxication. Although the mechanism remains unknown, involuntary movements similar to myoclonus should be considered as one of the extraordinary neurological manifestations of N2O intoxication.

Midlife risk factors for subtypes of dementia: a nested case-control study in Taiwan.

OBJECTIVE: To identify the midlife risk factors for subtypes of dementia newly developed later in life. METHODS: A nested case-control study was conducted on 157 demented cases and 628 comparison cases selected from 40,636 men and women who were enrolled from 1982 to 1992. Four comparison cases were frequency-matched on age, time at enrollment (within 6 months), gender, and residential township. Midlife risk factors included vascular risk factors (body mass index [BMI], total cholesterol, total triglycerides, blood glucose, cerebrovascular accident [CVA] history, diabetes mellitus history, and hypertension history), cigarette smoking, and alcohol consumption. Dementia assessments were ascertained through the computerized data linkage from National Health Insurance Database from 2000 to 2002 and clinically confirmed by neurologists or psychiatrists. Conditional logistic regression analysis was used to estimate the matched odds ratio (OR) and its 95% confidence intervals (CI) for each risk factor. RESULTS: A J-shaped relationship was observed between BMI (kg/m(2)) and dementia. The multivariate-adjusted ORs (95% CI) of developing dementia were 1.84 (1.02-3.33), 1.87 (1.08-3.23) and 2.44 (1.39-4.28), respectively, for BMIs of <20.5, 23.0-25.4, >or=25.5 compared with a BMI of 20.5-22.9 as the referent group (OR = 1.0). Similar findings were observed for Alzheimer disease (AD) and vascular dementia (VaD). The association between obesity (BMI >or=25.5) and both AD and VaD was statistically significant among cigarette smokers but not among nonsmokers. Additionally, history of CVA was a significant risk factor for VaD, but not for AD. CONCLUSION: Being underweight, being overweight, and a cerebrovascular accident in midlife may increase the risk of dementia in late life.

Increased risk of cerebral hemorrhage in Chinese male heavy drinkers with mild liver disorder.

BACKGROUND: Epidemiological evidence suggests that heavy alcohol consumption increases the risk for either stroke or liver disease. The goal of this study was to determine whether heavy drinkers with mild liver disorder (MLD) are at risk of hemorrhagic stroke. METHODS: All of the 524 patients recruited were males with a first-ever acute stroke and were consecutively admitted to the Tri-Service General Hospital between January 2000 and December 2001. The risk factors, liver function, stroke subtypes, and hemostatic factors were assessed among 68 patients defined as heavy drinker stroke (HDS) and 456 patients as non-heavy drinker stroke (NHDS). RESULTS: HDS patients had a significantly higher incidence of hemorrhagic stroke than NHDS patients. HDS patients were also associated with significantly higher occurrence of cigarette smoking, hyperuricemia, liver dysfunction, and significantly lower platelet counts. HDS patients with MLD were more likely to have hemorrhagic stroke (76.5%) than HDS patients without MLD (33.3%) and NHDS patients with (40.3%) or without (26.7%) MLD. HDS patients with MLD also exhibited a significantly higher glutamic oxaloacetic transaminase/glutamic pyruvic transaminase ratio (2.0 +/- 1.2) and lower platelet number (185,000 +/- 85,000 per microl) when compared with HDS patients without MLD (1.4 +/- 0.5; 206,000 +/- 59,000 per microl) and NHDS patients with (1.1 +/- 1.0; 256,000 +/- 97,000 per microl) or without (1.4 +/- 0.7; 216,000 +/- 68,000 per microl) MLD. CONCLUSIONS: HDS patients with MLD are at higher risk for hemorrhagic stroke in part due to the changes in hemostatic factors, although other factors may also contribute to hemorrhagic stroke.

Laryngeal reinnervation by ansa cervicalis nerve implantation for unilateral vocal cord paralysis in humans.

BACKGROUND: Ansa cervicalis (AC)-recurrent laryngeal nerve anastomosis (RLN) is usually not desirable for correction of paralytic dysphonia when it is difficult to find a viable distal stump of the recurrent laryngeal nerve. Nerve implantation of the thyroarytenoid muscle with the ansa cervicalis is a simple alternative method. STUDY DESIGN: Ten patients with unilateral vocal cord paralysis were prospectively designed to receive nerve implantation. A minimum period of 12 months after onset of paralysis was allowed to elapse to permit possible spontaneous reinnervation or compensation. Patients were followed long enough (at least 2 years) to determine if the procedure was successful. All patients were subjected to preoperative and postoperative voice recording, acoustic analysis, and videolaryngoscopy. Some of them underwent laryngeal electromyography. RESULTS: Ten patients underwent nerve implantation of the thyroarytenoid muscles by using the ansa cervicalis, and 8 of 10 (80%) had improved phonatory quality. Laryngeal electromyography showed that the procedure produced satisfactory reinnervation of the thyroarytenoid muscle. CONCLUSIONS: Nerve implantation of the thyroarytenoid muscle by the anso cervicalis is a simple and efficient alternative to nerve transfer if dense scarring at the cricothyroid articulation and lack of a viable distal stump of the recurrent laryngeal nerve preclude the procedure of nerve transfer. But careful selection of the appropriate candidate seems to be the earliest prerequisite for a successful procedure.

Nitric oxide induces prion protein via MEK and p38 MAPK signaling.

The prion diseases or transmissible spongiform encephalopathy, such as human Creutzfeldt-Jakob disease (CJD) and so-called mad cow disease, are attributed to the causative agent, the scrapie variant of prion protein (PrP(Sc)) which causes fatal neurodegeneration. To investigate if stresses such as nitric oxide (NO) induced the cellular isoform of prion protein (PrP(C)), lipopolysaccharide, and sodium nitroprusside were used to treat N2a and NT2 cells, which resulted in elevated levels of the PRNP mRNA and prion protein. The signaling pathway for the NO-induced PrP(C) production involved guanylyl cyclase, MEK, and p38 MAPK as shown by the effect of specific pharmacological inhibitors ODQ, PD98059, and SB203580, respectively. Knowing the PrP induction by the biologically existing stimulus, this study provides useful information about the possible cellular mechanism and strategies for the treatment of CJD.

Valproate pretreatment protects dopaminergic neurons from LPS-induced neurotoxicity in rat primary midbrain cultures: role of microglia.

Parkinson's disease is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic (DA) neurons in the substantia nigra. Accumulating evidence supports the notion that neuroinflammation is involved in the pathogenesis of this disease. Valproate (VPA) has long been used for the treatment of seizures and bipolar mood disorder. In vivo and in vitro studies have demonstrated that VPA has neuroprotective and neurotrophic actions. In this study, using primary neuron-glia cultures from rat midbrain, we demonstrated that VPA is a potent neuroprotective agent against lipopolysaccharide (LPS)-induced neurotoxicity. Results showed that pretreatment with 0.6 mM VPA for 48 h robustly attenuated LPS-induced degeneration of dopaminergic neurons as determined by [(3)H] dopamine uptake and counting of the number of TH-ir neurons. The neuroprotective effect of VPA was concentration-dependent and was mediated, at least in part, through a decrease in levels of pro-inflammatory factors released from activated microglia. Specifically, LPS-induced increase in the release of TNFa, NO, and intracellular reactive oxygen species was markedly reduced in cultures pretreated with VPA. These anti-inflammatory effects of VPA were time and concentration-dependent correlated with a decrease in the number of microglia. Thus, our results demonstrate that protracted VPA pretreatment protects dopaminergic neurons from LPS-induced neurotoxicity through a reduction in levels of released pro-inflammatory factors, and further suggest that these anti-inflammatory effects may be contributed by VPA-induced reduction of microglia cell number. Taken together, our study reinforces the view that VPA may have utility in treating Parkinson's disease.

Skeletal muscle dihydropyridine-sensitive calcium channel (CACNA1S) gene mutations in chinese patients with hypokalemic periodic paralysis.

BACKGROUND: Thyrotoxic periodic paralysis (TPP), familial periodic paralysis (FPP), and sporadic periodic paralysis (SPP) are common causes of hypokalemic periodic paralysis and have similar clinical presentations, thus possibly sharing the identical mutations. METHODS: We analyzed the role of the three known CACNA1S gene mutations (R528H, R1239H, and R1239G) in Chinese patients, including two FPP families, 36 TPP patients, 12 SPP patients, and their relatives. Fifty unrelated healthy subjects were also studied. Genomic DNA was prepared from the peripheral blood of all patients, their family members, and healthy subjects. Mutations of the CACNA1S gene were screened using polymerase chain reaction-based restriction analysis. RESULTS: Two FPP families had the R528H point mutation, but with incomplete penetrance occurring more commonly in men than in women. Only one SPP patient had a de novo mutation (R528H). None of the TPP patients had mutations in the three hot spots. CONCLUSION: Patients with FPP have R528H mutations in the CACNA1S gene. Only a few patients with SPP may share similar mutations with FPP. TPP patients do not carry any of the three known gene mutations.

Muscular dystrophy: from pathogenesis to strategy.

Muscular dystrophies are a genetically heterogeneous group of degenerative muscle disorders. It characterized by progressive muscle wasting and weakness of variable distribution and severity. There are several subgroups including Duchenne/Becker, fascioscapulohumeral, limb-girdle, oculopharngeal, and congenital muscular dystrophy. Diagnosis is dependent to the characteristic clinical features in distribution of predominant muscle weakness, disease course and age onset as well as variable serum concentration creatine kinase, muscle histology, and genetic inheritance. Nearly 30 genes and encoded proteins are known to give rise to various forms of muscular dystrophy. Development of new prospects therapy for the muscular dystrophies is a big challenge. The target of strategies is aimed at inducing of a functional protein and improving the function of muscle weakness. These strategies include gene, cell and pharmacological therapies. However, efficiency of systemic delivery vectors to targets, immune reaction to vector and gene products, and toxicity to vector that must be solved before an effective treatment is available.