INTRODUCTION:

Elevated intracranial pressure (ICP) is generally observed in brain injury and intracerebral hemorrhage (ICH) patients and is consistently associated with poor neurological outcome. Intracranial pressure variability (IPV) is a better predictor of long-term neurological outcome than mean ICP in traumatic brain injury patients. However, whether IPV regulates functional outcome in ICH patients has not been investigated. In the present study, we investigated the relationship between IPV and functional outcome in ICH patients and determined whether IPV is a valid predictor of neurological outcome in ICH patients.

METHODS:

A consecutive series of 56 patients with ICH were enrolled in this study. These patients underwent surgical treatments and were planted with an ICP monitor. The ICP was continuously recorded for 7days at one-hour intervals. The mean arterial blood pressure (MAP) and cerebral perfusion pressure (CPP) were also calculated. We used successive variation (SV) to represent IPV, which was calculated by averaging the difference in ICP between successive parameters. The short-term outcome was dichotomized into improved and deteriorated groups based on the changes in their Glasgow Coma Scale (GCS) score between admission and 30days after admission. The long-term outcome was evaluated by Glasgow Outcome Scale (GOS) at 12months after discharge from the hospital, and the patients were dichotomized into independent and dependent groups.

RESULTS:

The results showed that IPV was lower in the improved patient group and higher in patients with poorer outcome at 30days after ICH. There was a significant positive correlation between SV and short-term neurological outcome. We also found the in-patient mortality was significantly increased in the high IPV patient group (P=0.02), which was divided by the cutoff point using receiver operating characteristic (ROC) curve analysis. The univariate correlation analysis demonstrated that the IPV levels were positively correlated with mean ICP (R(2)=0.652, P=0.000), while were negatively correlated with CPP (R(2)=0.426, P=0.000). Increases in SV of ICP were a predictor of 30-day poor short-term outcome, but not for 12-month long-term outcome after adjusting for the potential confounders in a multivariable logistic regression model.

CONCLUSIONS:

The results suggest that high IPV is correlated with poorer outcome in ICH patients. Managing the ICP at an appropriate level during the early phase after ICH may improve functional outcome in ICH patients.

A patient with a mood disorder and a Parkinsonian syndrome with frontal cognitive impairment thought to resemble progressive supranuclear palsy defied precise diagnosis until the development of respiratory compromise, prompting consideration of the diagnosis of Perry syndrome. A mutation in the dynactin 1 gene confirmed the diagnosis. Few examples of this disorder, characterised by depression, Parkinsonism, and respiratory insufficiency, have been reported but it may be more commonly recognised with the availability of genetic testing. Perry syndrome needs to be considered in the differential diagnosis of Parkinsonism, particularly in autosomal dominant pedigrees. Diagnosis early in the disease course may facilitate monitoring and prompt intervention to avoid potentially fatal respiratory failure.

We describe a patient with zoster paresis and an MRI that revealed extensive spinal cord lesions from the upper cervical to the lower thoracic spinal cord. Importantly, the patient reported considerable spontaneous improvement in strength 2-3weeks after zoster. This report reveals a previously undescribed remarkable preponderance of MRI lesions far beyond the site of zoster rash and focal lower motor neuron weakness.

BACKGROUND:

Little is known about relationships between Cognitive Impairment (CI) and verbal fluency measures in patients with a Clinically Isolated Syndrome (CIS) suggestive of Multiple Sclerosis. The aim of this study was to assess the extent of verbal fluency deficits and their predictive value for the presence of a CI in a population of CIS patients.

METHODS:

CI was detected by the Rao's Brief Repeatable Battery (BRB) and the Stroop Test (ST) in 100 CIS patients. The BRB includes the Word List Generation (WLG) test for semantic verbal fluency. The FAS test was used to investigate phonemic verbal fluency. CI was defined as the failure in at least 3 tests on BRB (without WLG to exclude criterion contamination bias) and ST.

RESULTS:

Eleven patients failed in at least 3 of the BRB tests and were classified as cognitively impaired. The comparison of Receiver Operating Characteristic curves showed that the Area Under the Curve (AUC) of the WLG was not significantly different from the AUC of the FAS (0.787 vs 0.755; p=N.S.). A cut-off <17 words for the WLG achieved 64% of sensitivity and a 79% of specificity, and a cut-off <28 words achieved 82% of sensitivity and a 66% of specificity in discriminating patients with CI.

CONCLUSIONS:

Verbal fluency deficits occur early in the disease course and may predict the presence of CI in CIS patients.

While the role of mitochondria in aging has been well characterized, their involvement in motor neuron aging remains poorly understood. Thus, we performed an exhaustive ultrastructural study of mitochondria in motor neurons from aged rats that revealed dramatic alterations in the mitochondria of axon terminals at neuromuscular junctions, characterized by swelling, mitochondrial fusion and the presence of megamitochondria. These alterations were not observed in ventral horn motor neurons in the spinal cord of aged rats, which were only altered by the appearance of electron-dense bodies in the dilated matrix cristae. Using X-ray microanalytical techniques we demonstrated the presence of calcium in these bodies, suggesting Ca(2+) overload. Moreover, in motor neurons from aged rats, cytochrome c and activated caspase 3 were detected in the cytoplasm of axon terminals at neuromuscular junctions, factors implicated in the apoptosis. Active caspase 3 was also found in the nucleus, soma and axons of aged alpha motor neuron neurons, where it mainly associated with microtubules. The colocalization of dynein and cleaved caspase 3 in neuromuscular junctions is strongly suggestive of the retrograde transport of apoptotic factors to the soma. These results are consistent with the early stages of degeneration in neuromuscular junctions during aging, which is followed by dying back. Given that aging is a key risk factor for neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), the identification of age-related motor neuron degeneration initiated at the distal end of the axon may provide a new therapeutic target for early intervention.

Dabigatran, rivaroxaban, and apixaban are the new oral anticoagulants (NOAC) which have been investigated in patients with atrial fibrillation (AF) for primary and secondary prevention of stroke and thromboembolism. In these trials NOAC had a similar efficacy and safety profile compared to traditional vitamin-K-antagonists such as warfarin. We advise caution in the use of NOAC in patients with stroke or cerebral hemorrhage because of the following reasons: 1) Patients with cerebral bleeding were excluded from the trials. 2) Stroke within 14days and severe stroke within 6months before screening were exclusion criteria in the trials investigating dabigatran and rivaroxaban. 3) There is no antidote for reversal and no reliable laboratory monitoring of the anticoagulant effect for emergency situations. 4) NOAC are either substrates of the P-glycoprotein (P-gp) or are metabolized by the cytochrome P450 (CYP) system, or both. Drug-drug interactions between NOAC and P-gp and CYP-affecting drugs are largely unknown. 5) Long-term effects of thrombin generation inhibition on the occurrence of infections, malignancies, dementia, and other diseases are unknown. Based on these considerations it is our opinion that studies of NOAC in patients with stroke compared with other prevention strategies, as well as more post marketing surveillance data, are required.

BACKGROUND:

Cigarette smoking seems to contribute to susceptibility and progression of multiple sclerosis (MS).Although the incidence of MS in Iranian population has increased during recent years, the effects of smoking on progression of MS have not been studied. The aim of this study was to investigate the association between cigarette smoking and development of secondary progressive MS (SPMS) in Iranian patients with MS.

METHODS:

This study was carried out on patients registered in the MS Society (Guilan, Iran) database. Using a structured questionnaire, information on smoking status of 400 of patients could be obtained. The association between cigarettes smoking and SPMS was analyzed by Cox regression model.

RESULTS:

The relationship between smoking and development of SPMS was still evident after adjusting for age at disease onset, gender and number of relapses per year (P =0.004). Smoking more than 10 cigarettes per day increased risk of development of SPMS (HR: 2.43; 95% CI: 1.28 to 4.6; P =0.007).

CONCLUSIONS:

Our results indicated that smokers have an increased risk for progression of relapsing-remitting MS (RRMS) to SPMS compared with non-smokers. We also showed that the disease progression may be influenced by increase of cigarette smoking.

BACKGROUND:

Previous research suggested a relationship between low vitamin D and relapse rate. We examined whether vitamin D levels were associated with: 1) MS severity and 2) recent MS relapse activity, in patients treated with natalizumab.

METHODS:

All patients (n=118) were treated with natalizumab and were tested for vitamin D levels during the winter of 2009-10. Number of relapses during treatment with natalizumab was determined by retrospective chart review. MS severity was estimated with the Roxburgh's MS Severity Score (MSSS) at the time of the initial blood draw and 1year preceding and following initial draws. Vitamin D levels of 50nmol/L or greater were defined as normal.

RESULTS:

Patients with deficient vitamin D levels (DVD) totaled 45. Sixteen of the 26 patients with relapse in the year prior to the initial blood draw (4 patients had multiple relapses - all were in DVD) and 12 of 17 patients with relapse in the following year were in the DVD group. There was a significant difference between the normal vitamin D group (NVD) and DVD in MS relapse activity in the year prior (p=0.005) and following blood draw (p=0.006). There was no significant between group differences in MSSS at any time.

CONCLUSIONS:

Natalizumab treated patients with DVD were more likely to experience relapse and may experience more relapses than patients with NVD.

The differences in non-motor symptoms (NMS) along with the duration of Parkinson's disease (PD) in Chinese populations remain largely unknown. A total of 616 PD patients consisting of 189 patients with disease duration of less than 2years, 239 patients with duration between 2 and 5years, 122 patients with duration between 5 and 10years, and 66 patients with duration more than 10years from Southwest China were studied. Each patient was assessed using the non-motor symptoms scale (NMSS). The mean affected number of NMS was 8.8±5.8, and the mean total NMSS score was 36.3±33.2. The mean affected number of NMS and the mean total NMSS score increased with the disease progression. The following symptoms became more common and severe with the disease duration: falls due to fainting, fatigue, difficulty falling asleep, restless legs, perceptual problem/hallucination domain (i.e., "hallucinations," "delusions," and "double vision"), gastrointestinal domain (i.e., "dribbling saliva," "swallowing," and "constipation"), urinary domain (i.e., "urgency," "frequency," and "nocturia"), and miscellaneous domain (i.e., "excessive sweating"). However, some symptoms such as mood/apathy pleasure, sexual dysfunction, and others remained stable. NMS are prevalent in all disease duration of the Chinese PD patients. Although the mean affected number of NMS and NMMS score increased with the disease duration, NMS progression is symptom specific.

Brain metal accumulation is suggested in the pathogenesis of numerous neurodegenerative disorders. In Wilson's disease (WD), only copper has been examined. The aim of the present study was to evaluate the copper, iron, manganese, and zinc concentrations in autopsy tissue samples from the brains of WD patients.The study material consisted of 17 brains (12 WD patients, 5 controls) obtained at autopsy. Samples were taken from four different regions of each brain: frontal cortex, putamen, pons, and nucleus dentatus. The copper, manganese, and zinc content were determined using inductively coupled plasma mass spectrometry, and iron was assessed using flame atomic absorption spectroscopy. The results were analyzed according to select clinical variables.Copper content was increased homogenously in all investigated structures of the WD brains compared to controls (41.0±18.6μg/g vs.5.4±1.8μg/g; P<0.01). The mean concentrations of iron, manganese, and zinc were similar in WD and controls, but the iron level in the nucleus dentatus was higher in WD compared to controls (56.8±14.1μg/g vs. 32.6±6.0μg/g; P<0.05). Gender, age, and type and duration of WD treatment did not impact brain metals storage, but some correlations between the duration of the disease and copper and iron accumulation were observed.During the course of WD, copper accumulates equally in different parts of the brain. Zinc and manganese do not seem to be involved in WD pathology, but increased levels of iron were found in the nucleus dentatus. Thus, additional studies of brain iron accumulation in WD are needed.