SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome.

Linkage analysis and DNA sequencing in a family exhibiting an X-linked mental retardation (XLMR) syndrome, characterized by microcephaly, epilepsy, ataxia, and absent speech and resembling Angelman syndrome, identified a deletion in the SLC9A6 gene encoding the Na(+)/H(+) exchanger NHE6. Subsequently, other mutations were found in a male with mental retardation (MR) who had been investigated for Angelman syndrome and in two XLMR families with epilepsy and ataxia, including the family designated as having Christianson syndrome. Therefore, mutations in SLC9A6 cause X-linked mental retardation. Additionally, males with findings suggestive of unexplained Angelman syndrome should be considered as potential candidates for SLC9A6 mutations.

Nerve conduction, visual evoked responses and electroretinography in tunnel workers previously exposed to acrylamide and N-methylolacrylamide containing grouting agents.

The study examines possible persisting effects on the peripheral nervous system and visual system in tunnel workers previously exposed to acrylamide and N-methylolacrylamide during grouting work. We compared neurophysiological function in 44 tunnel workers previously exposed during grouting operations (2-10 years post exposure), with 49 tunnel workers with no history of exposure to acrylamide. Nerve conduction velocities (NCV), distal delay, F-response and amplitude in median and ulnar nerves of the right arm, peroneal, sural and tibial nerves of the right leg, visual evoked response (VER) and electroretinography (ERG) were measured. VER and ERG were also performed in 24 subjects more recently exposed to acrylamide grout (16 months post exposure). Exposure to acrylamide containing grouts was assessed by questionnaires. A statistically significant reduction in the mean sensory NCV of the sural nerve (p=0.005), as well as a non-significant reduction of sural amplitude was found in the previously exposed group compared to the control group. VER latencies to the onset of the occipital potential (N75) were prolonged in both exposed groups compared to the control group (p<0.05). ERG 30 Hz flicker amplitude was reduced in the recently exposed group compared to the referents (p<0.05). The results indicate slight subclinical, but persistent toxic effects in the sural nerve and the visual system in tunnel workers exposed to N-methylolacrylamide and acrylamide during grouting operations.

Determination of prognosis after cardiac arrest may be more difficult after introduction of therapeutic hypothermia.

A 50-year-old patient had status epilepticus and no adequate reactions nine days after prolonged out-of-hospital cardiac arrest. The cause of the arrest was acute myocardial infarction which was treated successfully with percutaneous cardiac intervention (PCI) and a stent placement. He was treated with therapeutic hypothermia (33 degrees C) for 24h and in intensive care with respiratory support for 42 days. One year later he has fully recovered and is back to normal life and academic work. The previously reported 100% prognosis of a poor neurological outcome in the presence of seizures 72 h post arrest may need to be re-examined after introduction of therapeutic hypothermia.

Fatigue in patients with lupus is not associated with disturbances in cerebral blood flow as detected by SPECT.

OBJECTIVES: Fatigue is a common complaint in patients with systemic lupus erythematosus (SLE). We investigated whether focal or general disturbances of cerebral blood flow (CBF), as assessed by SPECT, were associated with the presence of fatigue in an unselected group of SLE patients. METHODS: Fifty-six patients were included. Mean age was 47.5 years (+/-12.7), mean disease duration 14.7 years (+/-8.9), and disease activity measured by SLE disease activity index (SLEDAI) was 5.7 (+/-5.4). Fatigue was assessed by the Fatigue Severity Scale (FSS) and CBF by Tc-99m-hexamethyl propylamine oxime (HMPAO)-SPECT. The images were read and processed quantitatively by a computer program using the primary visual cortex as reference region and > 15% CBF deviation as definition of abnormality. RESULTS: The mean FSS score was 4.6 (+/-1.8). SPECT revealed focal CBF disturbances in 17 patients (30.4 %). Generalized symmetrical CBF reductions were present in 32 patients (57.1 %). There were no significant associations between CBF disturbances in any region of the brain and the degree of fatigue. CONCLUSIONS: Fatigue in SLE patients is not related to focal or general CBF disturbances. Therefore, factors that do not influence blood flow seem responsible for the fatigue phenomenon.

Optimal blood glucose control during 18 years preserves peripheral nerve function in patients with 30 years' duration of type 1 diabetes.

OBJECTIVE: To assess the association between 18 years of mean HbA(1c) and nerve conduction parameters of the lower limb in patients with type 1 diabetes of 30 years' duration. RESEARCH DESIGN AND METHODS: HbA(1c) has been examined prospectively since 1982 in a group of 39 patients with type 1 diabetes. Mean age at baseline was 25 years (range 18-40) with 12 years' disease duration. The mean age at diagnosis of diabetes was 12.5 years. Nerve function of lower limbs was assessed at baseline, after 8 years, and after 18 years. RESULTS: A total of 23 men and 16 women were studied. Mean age was 43 years. Mean HbA(1c) was 8.2% (range 6.6-11.3) during 18-year follow-up. Nerve conduction velocity (NCV) and nerve action potential amplitude (NAPA) at the last examination were significantly associated with mean HbA(1c) (P < 0. 05). From 1982 to 1999, there was a significant reduction in nerve function in patients with mean HbA(1c) >or=8.4% (highest tertile). For example, the mean NCV in the tibial nerve was reduced from 47 to 31 m/s (P < 0.01). The number of nerves with NCV (P < 0.01) and NAPA (P = 0.01) reduced to below the reference level in each patient was also significantly associated to mean HbA(1c). No significant associations were found between nerve function parameters, sex, disease duration, blood pressure, serum cholesterol, microalbuminuria, or smoking. CONCLUSIONS: The present study shows that mean HbA(1c) is a strong predictor of nerve function. Mean HbA(1c) <8.4% over 18 years was associated with near-normal nerve function.

Eighteen years of fair glycemic control preserves cardiac autonomic function in type 1 diabetes.

OBJECTIVE: To study the association between 18 years of mean HbA(1c) and cardiac autonomic function in type 1 diabetic patients having used intensive insulin treatment. RESEARCH DESIGN AND METHODS: A total of 39 patients with type 1 diabetes were followed during 18 years, and HbA(1c) was measured yearly. At 18 years follow-up heart rate variability (HRV) measurements were used to assess cardiac autonomic function. Standard cardiac autonomic tests during normal breathing, deep breathing, the Valsalva maneuver, and the tilt test were performed. Maximal heart rate increase during exercise electrocardiogram and minimal heart rate during sleep were also used to describe cardiac autonomic function. RESULTS: We present the results for patients with mean HbA(1c) <8.4% (two lowest HbA(1c) tertiles) compared with those with HbA(1c) > or = 8.4% (highest HbA(1c) tertile). All of the cardiac autonomic tests were significantly different in the high- and the low-HbA(1c) groups, and the most favorable scores for all tests were seen in the low-HbA(1c) group. In the low-HbA(1c) group, the HRV was 40% during deep breathing, and in the high-HbA(1c) group, the HRV was 19.9% (P = 0.005). Minimal heart rate at night was significantly lower in the low-HbA(1c) groups than in the high-HbA(1c) group (P = 0.039). With maximal exercise, the increase in heart rate was significantly higher in the low-HbA(1c) group compared with the high-HbA(1c) group (P = 0.001). CONCLUSIONS: Mean HbA(1c) during 18 years was associated with cardiac autonomic function. Cardiac autonomic function was preserved with HbA(1c) <8.4%, whereas cardiac autonomic dysfunction was impaired in the group with HbA(1c) > or = 8.4%.

123I-beta-CIT SPECT demonstrates increased presynaptic dopamine transporter binding sites in basal ganglia in vivo in schizophrenia.

RATIONALE: The dopamine hypothesis for schizophrenia postulates overactivity of dopamine transmission in the basal ganglia. Most effective antipsychotic drugs block postsynaptic dopamine receptors, but in-vivo imaging studies have not been able to show changes in these receptors in drug-naive schizophrenics. OBJECTIVES: The presynaptic dopamine transporter (DAT) is thought to be an important regulator of synaptic dopamine concentration. We have used SPECT with (123)I-beta-CIT, which has a high affinity for DAT, in order to further examine the dopamine hypothesis for schizophrenia. METHODS: Six patients with chronic schizophrenia treated with classic dopamine D(2)-receptor blocking neuroleptics were investigated. The number of DAT binding sites in the basal ganglia was calculated and compared with five healthy volunteers and ten parkinsonian patients. RESULTS: The schizophrenic patients showed a 36-63% increase in DAT binding sites compared with the volunteers, whereas the parkinsonian patients showed a 57-96% decrease. The differences between the groups were highly significant (even after correction for different age composition within the groups). CONCLUSIONS: There was an increased number of DAT binding sites in the schizophrenic patients treated with dopamine D(2)-receptor blocking neuroleptics. This fits well with several recent reports that have shown increased volumes of basal ganglia in this patient category. It thus appears that there is an increased number of presynaptic dopamine releasing nerve terminals in the basal ganglia, possibly as a biological adaptation to counteract the postsynaptic dopamine D(2)-receptor blockade.

Effects on the peripheral nervous system of tunnel workers exposed to acrylamide and N-methylolacrylamide.

OBJECTIVES: This study evaluates the possible toxic effects on the peripheral nervous system of tunnel workers exposed to acrylamide and N-methylolacrylamide during grouting work. METHODS: Symptoms and nerve conduction velocities (NCV) were recorded for 24 tunnel workers 4 and 16 months after the cessation of exposure during grouting operations. Fifty tunnel workers not involved in grouting operations served as referents. Exposure was assessed by questionnaires, qualitative exposure indices, and measurements of hemoglobin adducts after the cessation of exposure. RESULTS: The exposed workers reported a higher prevalence of symptoms during grouting work than they did in an examination 16 months later. A statistically significant reduction in the mean sensory NCV of the ulnar nerve was observed 4 months postexposure when compared with the values of the reference group (52.3 versus 58.9 m/s, P = 0.001), and the mean ulnar distal delay was prolonged (3.1 versus 2.5 ms, P = 0.001). Both measures were significantly improved when measured 1 year later. Exposure-related improvements were observed from 4 to 16 months postexposure for both the median (motor and sensory NCV and F-response) and ulnar (sensory NCV, F-response) nerves. A significant reversible reduction in the mean sensory amplitude of the median nerve was also observed, while the mean sensory amplitude of the sural nerve was significantly reduced after 16 months. CONCLUSIONS: The results indicate demyelinating and axonal changes in peripheral nerves of tunnel workers in relation to exposure to N-methylolacrylamide and acrylamide during grouting operations. The changes were slight, mostly subclinical, and most of the effects were reversible, with normalization after 1 year.

Serial single-photon emission computed tomographic and transcranial doppler measurements for evaluation of vasospasm after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To assess the clinical value of serial single photon-emission computed tomographic (SPECT) measurements after aneurysmal subarachnoid hemorrhage (SAH). METHODS: Thirty-two patients were studied prospectively during the first 26 days after SAH with repeated SPECT measurements, clinical examinations, and transcranial Doppler recordings. Time trends were analyzed with a general linear model. A final SPECT measurement was performed after 1 year. RESULTS: A mean of 2.6 (range, 1-5) SPECT measurements revealed a significant (P = 0.001) quadratic curve consistent with initial hypoperfusion and then with hyperperfusion during the acute stage. SPECT findings were significantly associated with transcranial Doppler recordings (P = 0.016) and clinical assessments (P = 0.008). Patients fulfilling clinical and transcranial Doppler criteria for vasospasm demonstrated a more pronounced relative hypoperfusion-hyperperfusion time course. A multivariate logistic regression analysis identified SPECT measurements obtained during Days 7 to 14 after the SAH as the only independent predictor (beta = 0.042, P = 0.02) for impaired perfusion after 1 year. CONCLUSION: Serial SPECT measurements after aneurysmal SAH demonstrate that regional changes in cerebral perfusion follow a nonlinear time trend, and repeated measurements are necessary. This observation, as well as the low feasibility of SPECT, restricts the clinical value of such measurements.