Autosomal-dominant striatal degeneration is caused by a mutation in the phosphodiesterase 8B gene.

Autosomal-dominant striatal degeneration (ADSD) is an autosomal-dominant movement disorder affecting the striatal part of the basal ganglia. ADSD is characterized by bradykinesia, dysarthria, and muscle rigidity. These symptoms resemble idiopathic Parkinson disease, but tremor is not present. Using genetic linkage analysis, we have mapped the causative genetic defect to a 3.25 megabase candidate region on chromosome 5q13.3-q14.1. A maximum LOD score of 4.1 (Theta = 0) was obtained at marker D5S1962. Here we show that ADSD is caused by a complex frameshift mutation (c.94G>C+c.95delT) in the phosphodiesterase 8B (PDE8B) gene, which results in a loss of enzymatic phosphodiesterase activity. We found that PDE8B is highly expressed in the brain, especially in the putamen, which is affected by ADSD. PDE8B degrades cyclic AMP, a second messenger implied in dopamine signaling. Dopamine is one of the main neurotransmitters involved in movement control and is deficient in Parkinson disease. We believe that the functional analysis of PDE8B will help to further elucidate the pathomechanism of ADSD as well as contribute to a better understanding of movement disorders.

Treatment for obstructive sleep apnoea: effect on peripheral nerve function.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) is suggested to be associated with peripheral nerve damage. A case-control study was conducted to provide further support to this observation. In a longitudinal intervention study, it was examined whether treatment for OSA has a possible beneficial effect on peripheral nerve function. METHODS: Participants were 23 patients with OSA and 23 controls matched for age and body mass index (BMI), all without any known cause of peripheral nerve damage. The sensory nerve action potential (SNAP) amplitudes of both sural nerves were determined. After 6 months of treatment for OSA, treatment compliance was evaluated and nerve conduction studies were repeated. RESULTS: Patients with OSA had significantly lower mean (standard deviation) sural SNAP amplitudes than controls (6.3 (3.5) v 11.2 (5.0), p < 0.001). Multivariate regression analysis including the variables age, BMI and Apnoea-Hypopnea Index (AHI) showed that both age (p < 0.01) and AHI (p < 0.05) were inversely related to the SNAP amplitude. On follow-up, the sural SNAP showed an increase of 2.6 mV on average (p < 0.001). Multivariate regression analysis including the variables age, BMI, AHI, pretreatment SNAP and treatment compliance identified only treatment compliance as being significantly related to the SNAP increase (p < or = 0.005). CONCLUSION: OSA is an independent risk factor for axonal dysfunction of peripheral sensory nerves. Impaired neural function is at least partly reversible with treatment for sleep apnoea.

Night-time bradyarrhythmia in a patient with mild obstructive sleep apnea syndrome is reversed with CPAP treatment.

Nocturnal cardiac arrhythmia is a common clinical feature of obstructive sleep apnea syndrome. Pathologically relevant rhythm disturbances such as atrioventricular block or ventricular tachycardia are known to occur mainly in patients with a high apnea-hypopnea index and marked oxygen desaturation. We report on a patient with mild obstructive sleep apnea syndrome who nevertheless showed intermittent second-degree atrioventricular block during stages of rapid eye movement sleep-associated hypopneas. Cardiac arrhythmia was reversed with the initiation of nasal continuous positive airway pressure treatment. Based on this case report and taking into account known facts from the literature, the finding of intermittent second-degree atrioventricular block in our patient with mild obstructive sleep apnea syndrome supports careful evaluation of electrocardiogram recording acquired during polysomnography in all patients with suspected obstructive sleep apnea syndrome.

The prognostic value of [F]FDG-PET in nonrefractory partial epilepsy.

PURPOSE: Regional abnormalities of cerebral glucose metabolism, as identified by 18-fluorodeoxyglucose positron emission tomography (FDG-PET) have prognostic value regarding the outcome of epilepsy surgery in patients with refractory partial epilepsy. The value of FDG-PET abnormalities in nonrefractory patients has not been investigated systematically. This study examines whether FDG-PET could be used for early identification of nonrefractory epilepsy in patients who will become pharmacoresistant later during the course of their disease. METHODS: We investigated interictal abnormalities of cerebral glucose metabolism by using FDG-PET in 125 consecutive patients with nonrefractory cryptogenic partial epilepsy and normal cranial magnetic resonance imaging (MRI), and we compared relative changes in seizure frequency in 90 patients after > or =2 years of follow-up. RESULTS: Regional asymmetry of tracer distribution was seen in 43 of the 90 patients. Forty-one patients had regional glucose hypometabolism in the temporal and two patients in an extratemporal region. No difference between patients with and without a hypometabolic focus was found regarding seizure freedom after follow-up. This held true also for the subgroup of patients with epilepsy onset within 1 year before admission. Only patients with regional glucose metabolism showed an increase in seizure frequency. Multivariate analysis showed that only anticonvulsive treatment before index admission and the possibility of localizing the epileptogenic focus by using all available clinical and EEG data were independently associated with continuing seizures after a median follow-up period of 43 months. CONCLUSIONS: Regional hypometabolism in FDG-PET is not significantly associated with a lower likelihood of successful anticonvulsant drug therapy in patients with nonrefractory partial epilepsy. Careful analysis of all routinely available clinical and neurophysiologic data has a much better predictive power to identify patients with medically refractory epilepsy early in the course of the disease. However, if PET data are available, they could help in identifying patients with a less benign course.

Increased prevalence of sleep apnea in patients with recurring ischemic stroke compared with first stroke victims.

Since sleep apnea (SA) and stroke have many shared risk factors an independent contribution of SA to the overall risk of stroke is not easily proven and has been questioned recently. To contribute to this controversy, we analysed the frequency of SA in groups of patients with first and recurring ischemic stroke. We prospectively studied 102 patients admitted to our stroke unit. The prevalence of vascular risk factors and a history of previous stroke were recorded. All patients received cardio-respiratory polygraphy during the first 72 hours after admission. CT and MRI scans were evaluated for the location of the acute stroke and the presence of older vascular lesions. Thirty-four women and 68 men with a mean age of 64.5 +/- 13.7 years were included in the study. Cerebral lesions attributable to a previous stroke were identified in 25 patients, of whom 19 reported to have suffered a stroke before. Patients with stroke recurrence had a higher mean apnea-hypopnea index (AHI) (26.6/h vs. 15.1/h, p<0.05) and more often presented with a sleep apnea syndrome (SA) defined by an AHI >or=10/h (80 vs. 52%, p < 0.05) than patients with first ever stroke. Logistic regression analysis including the variables "age", "gender", "cumulative risk factors", "AHI >or=10/h", and "diabetes" identified diabetes (Odd's ratio [OR]=4.5) and AHI >or=10/h (OR=3.5) as independent risk-factors for stroke recurrence. According to our results SA is an independent risk factor for stroke recurrence. We therefore advocate routine sleep-apnea screening in all patients having suffered an ischemic stroke.

Serial proton spectroscopy in a case of adult-onset subacute sclerosing panencephalitis.

A case of subacute sclerosing panencephalitis in a 27-year-old man was serially evaluated with proton magnetic resonance spectroscopy. Metabolic abnormalities included decreased N-acetylaspartate and elevated choline and myo-inositol in a lesion visible on magnetic resonance imaging and in normal-appearing white matter. Lactate appeared increased within the lesion. Metabolic impairment was persistent after intrathecal interferon-alpha treatment. Spectroscopy pointing to ongoing inflammation, gliosis, and possible membrane turnover was more sensitive than imaging in detecting widespread pathology within the white matter.

Capnography screening for sleep apnea in patients with acute stroke.

Sleep apnea syndrome (SAS) is a prominent clinical feature in acute stroke patients. Diagnosis is usually established by polysomnography or cardio-respiratory polygraphy (CRP). Both diagnostic procedures produce high costs, are dependent on the access to a specialized sleep laboratory, and are poorly tolerated by patients with acute stroke. In this study we therefore investigated whether capnography may work as a simple screening tool in this context. In addition to conventional CRP, 27 patients with acute stroke were studied with capnography provided by our standard monitoring system. The trend graphs of the end-tidal CO(2) values (EtCO(2)) were used to determine the capnography-based estimate of the apnea-hypopnea index (AHI(CO2)). Index events were scored when the EtCO(2) value dropped for > 50% of the previous baseline value. We found that the AHI(CO2) correlated significantly with the apnea-hypopnea index measured with conventional CRP (AHI(CRP)) (r = 0.94; p < 0.001). An AHI(CO2) > 5 turned out to be highly predictive of an AHI(CRP) > 10. According to our findings, routinely acquired capnography may provide a reliable estimate of the AHI(CRP). The equipment needed for this screening procedure is provided by the monitoring systems of most intensive care units and stroke units where stroke patients are regularly treated during the first days of their illness. Therefore, early diagnosis of SAS in these patients is made substantially easier.

Cervical artery dissection--clinical features, risk factors, therapy and outcome in 126 patients.

The highly variable clinical course of cervical artery dissections still poses a major challenge to the treating physician. This study was conducted (1) to describe the differences in clinical and angiographic presentation of patients with carotid and vertebral artery dissections (CAD, VAD), (2) to define the circumstances that are related to bilateral arterial dissections, and (3) to determine factors that predict a poor outcome. Retrospectively and by standardised interview, we studied 126 patients with cervical artery dissections. Preceding traumata, vascular risk factors, presenting local and ischemic symptoms, and patient-outcome were evaluated. Patients with CAD presented more often with a partial Horner's syndrome and had a higher prevalence of fibromuscular dysplasia than patients with VAD. Patients with VAD complained more often of neck pain, more frequently reported a preceding chiropractic manipulation and had a higher incidence of bilateral dissections than patients with CAD. Bilateral VAD was significantly related to a preceding chiropractic manipulation. Multivariate analysis showed that the variables stroke and arterial occlusion were the only independent factors associated with a poor outcome. This study emphasises the potential dangers of chiropractic manipulation of the cervical spine. Probably owing to the systematic use of forceful neck-rotation to both sides, this treatment was significantly associated with bilateral VAD. Patients with dissection-related cervical artery occlusion had a significantly increased risk of suffering a disabling stroke.

The prognostic impact of clinical and CT parameters in patients with pontine hemorrhage.

BACKGROUND: In patients with pontine hemorrhage (PH), an accurate prognostic assessment is critical for establishing a reasonable therapeutic approach. METHODS: The initial clinical symptoms and computed tomography (CT) features were analyzed with multivariate regression analysis in 39 consecutive patients with PH. PHs were classified into three types: (1) large paramedian, (2) basal or basotegmental and (3) lateral tegmental, and the hematomas' diameters were measured. The patients' outcome was evaluated. RESULTS: Twenty-seven patients (69%) died and 12 (31%) survived for more than 1 year after PH. The symptom most predictive of death was coma on admission. The large paramedian type of PH predicted a poor prognosis, whereas the lateral tegmental type was associated with a favorable outcome. The transverse hematoma diameter was also related to outcome, with the threshold value found to be 20 mm. CONCLUSIONS: We conclude that PH outcome can be estimated best by combining the CT parameters 'large paramedian PH' and 'transverse diameter >/=20 mm' with the clinical variable 'coma on admission'. Survival is unlikely if all 3 features are present, whereas survival may be expected if only 1 or none of these features is found.

Painless legs and moving toes in a mother and her daughter.

Painful legs and moving toes (PLMT) is a rare syndrome which is characterised by involuntary movements of the toes and pain in the legs. We report on a mother and her daughter who both presented with involuntary movements of the toes similar to those seen in PLMT but without any associated pain. Neurological examination revealed intermittent 0.3 to 0.5-Hz flexion and extension of the toes and ankles of the right foot in the mother, and of both feet in the daughter. In both patients, the movements appeared during periods of rest that were uncorrelated with the time of day. Diagnostic work-up gave no evidence of radiculopathy or of focal neuropathy. Overnight polysomnography documented that movements of the toes and feet occurred only before sleep onset and during periods of nocturnal awakening or arousals. Because the movements observed in our patients were similar to those seen in patients with PLMT, we diagnosed an abortive form of this syndrome, which already has got the naming "painless legs and moving toes." The occurrence in a mother and her daughter may point to a hereditary component of this disorder.

Placing nasogastric tubes and intracranial pressure.

Recently, a new method for placing nasogastric tubes (NGT) in dysphagic patients was proposed, which uses the swallowing reflex and was therefore called 'reflex placement.' The authors describe the use of this method in a patient with a large left sided striatocapsular hemorrhage, in whom decompressive craniotomy had been performed previously. Whereas the conventional approach of placing NGT led to a massive increase of intracranial pressure (ICP) and to a decline in cerebral perfusion pressure (CPP), the new method allowed a swift placement with only minor changes of ICP and CPP. The strict avoidance of intermittent peaks of ICP constitutes a basic principle of care in patients with space occupying brain lesions. We therefore suggest that, despite the admittedly larger effort, the reflex placement of NGTs should be used in such circumstances.

The association between disease severity and sleep-related problems in patients with Parkinson's disease.

Although sleep-related problems are a frequent finding in patients with Parkinson's disease (PD), the aetiology is still unknown. We examined the associations between disease severity, sleep-related problems and social status in 116 PD patients participating in the FAQT Study, a prospective, German cohort study evaluating determinants of quality of life in PD patients. 47.4% of the patients reported sleep onset difficulties, 26.7% sleep interruptions, 14.7% had five or more sleep-related events during the night and 71.6% showed symptoms of increased daytime somnolence. The disease severity was significantly associated with sleep-related events (p = 0.01), the depression score with sleep onset difficulties (p = 0.04), sleep interruptions (p = 0.01) and the levodopa dose (p < 0.01). We conclude that depressive symptoms and increasing levodopa doses in PD patients mainly cause sleep onset difficulties and sleep interruptions, while the severity of motor symptoms contributes to sleep-related events like sleep walking, heavy sweating and nightmares.

Late onset postpartum eclampsia: a rare and difficult diagnosis.

Late postpartum eclampsia without the classical pre-eclamptic signs oedema, proteinuria and hypertension is a rarely noticed complication of pregnancy. In three patients eclampsia started no earlier than 6, 8 and 11 days postpartum. Seizures were preceded by headache, vomiting, visual disturbance or impaired level of consciousness. One patient suffered a series of seizures making neurointensive care necessary. In another patient the clinical course was complicated by an additional Guillain-Barré syndrome. Aside from the typical parieto-occipital lesions brain MRI showed cerebellar hyperintensities on T2 weighted sequences as well as abnormalities on diffusion weighted images in one patient. In all patients neurological deficits and MRI findings were reversible.

Follow-up examinations by transcranial Doppler ultrasound in primary angiitis of the central nervous system.

BACKGROUND: Primary angiitis of the central nervous system (PACNS) is a rare disease. The definite diagnosis is made upon proof of mononuclear inflammation of the vessel wall on brain biopsy. The diagnosis can also be established on clinical grounds, typical findings on intra-arterial angiography and other investigatory grounds excluding other diseases. Therapy comprises an aggressive immunosuppressive approach. Close monitoring of the patients is mandatory. Transcranial Doppler ultrasound (TCD) has not yet been used to follow up the vasculitic lesions in PACNS. CASE: We report on a 32-year-old female with massive cerebral infarctions secondary to multiple large-vessel stenoses because of probable PACNS. The patient was followed closely by means of TCD. During therapy the cerebral blood flow velocities normalized as displayed by TCD. Clinical improvement followed several days after normalization of cerebral blood flow. CONCLUSIONS: TCD is a valuable noninvasive bedside tool to monitor cerebral blood flow velocities and therapy response in patients with cerebral vasculitis, if large arteries are involved.

Nonconvulsion status epilepticus in patients with juvenile myoclonic epilepsy: types and frequencies.

Juvenile myoclonic epilepsy (JME) is an idiopathic, age-related generalized epileptic syndrome, featuring generalizedtonic-clonic and absence seizures as well as myoclonic jerks. Except for some case reports, little is known about type and frequency of nonconvulsive status epilepticus (NCSE) in adult patients with JME. In a retrospective study we therefore reviewed all patients with JME, who had been referred to our hospital between 1994 and 1999 for the occurrence of NCSE. Of the 69 patients with JME seen within these 6 years three women had typical absence status-one of them two times-and one woman had impulsive-petit-mal status. All four patients had a history of myoclonic, absence and generalized tonic-clonic seizures. Because of the extreme rarity of impulsive-petit-mal status the corresponding case history is presented in detail. According to our findings the prevalence of NCSE in JME can be estimated at 5.8%, the incidence at 1.2% per year with a clear preponderance of female gender.

Hypoglossal nerve palsy as complication of oral intubation, bronchoscopy and use of the laryngeal mask airway.

Hypoglossal nerve injury is a recognized but rare complication of oropharyngeal manipulation during intubation, bronchoscopy and use of a laryngeal mask airway. We present 2 new cases of temporary hypoglossal nerve palsy after orotracheal intubation for general anesthesia. The relevant literature is reviewed and different hypotheses concerning the pathophysiological mechanisms of nerve damage are discussed.

Tiagabine-related non-convulsive status epilepticus in partial epilepsy: three case reports and a review of the literature.

There have been several recent reports of non-convulsive status epilepticus during tiagabine therapy in patients with partial epilepsy. We report three cases where elevation of tiagabine dosage was followed by electroclinical features, or electroencephalographic features without clinical signs, of non-convulsive status epilepticus. Administration of clonazepam and/or discontinuation to tiagabine lead to complete remission. In one case after re-exhibition of tiagabine the EEG again showed rhythmic delta waves. We review the other cases reported so far and discuss the different pathophysiological hypotheses about the association in the light of new experimental data.