Brain microvascular pericytes in health and disease

Pericytes are located at periphery of the microvessel wall and wrap it with their processes. They communicate with other cells of the neurovascular unit by direct contact or through signaling pathways and regulate several important microcirculatory functions. These include development and maintenance of the blood–brain barrier (BBB), distribution of the capillary blood flow to match the local metabolic need of the nearby cells, and angiogenesis. Pericytes also exhibit phagocytic activity and may function as pluripotent stem cells. Increasing evidence suggests a role for pericytes in a wide range of CNS diseases. They appear to be vulnerable to oxygen and nitrogen radical toxicity and have been shown to contract during cerebral ischemia and remain contracted despite reopening of the occluded artery. This causes impaired re-flow and may diminish the benefit of re-canalization therapies in stroke patients. Hyperglycemia-induced dysfunction of the signaling pathways between pericytes and endothelia is thought to play an important role in diabetic retinopathy, a common cause of blindness. Amyloid deposits detected within degenerating pericytes in the brains of patients with Alzheimer’s disease suggest that pericyte dysfunction may play a role in cerebral hypoperfusion and impaired amyloid β-peptide clearance in Alzheimer’s disease. This exciting possibility may reveal a novel temporal sequence of events in chronic neurodegeneration, in which microvascular dysfunction due to pericyte degeneration initiates secondary neurodegenerative changes. Identification of molecular mechanisms by which pericytes regulate BBB integrity in inflammatory conditions as well as in vasogenic brain edema may lead to new treatments. Pericytes may also take part in tissue repair and vascularization after CNS injury. In conclusion, although the evidence is just emerging and mostly preliminary, disclosing pericytes’ role in the pathophysiology of CNS diseases may yield exciting developments and novel treatments.     

Is multiple sclerosis a risk factor for atherosclerosis?

BackgroundMultiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. We aimed to discuss possible predisposing factors to atherosclerosis such as carotid intima-media thickness (CIMT) and high-sensitivity C-reactive protein (Hs-CRP) levels in MS.MethodsThirty-five ambulatory patients with relapsing-remitting MS (RRMS) (22 females and 13 males) and 34 healthy controls (21 females and 13 males) with similar demographic variables were included. Blood cell counts, cholesterol levels, vitamin D and B12, Hs-CRP levels, body mass index (BMI), history of smoking, and CIMT of both groups, Expanded Disability Status Scale (EDSS) scores, and disease duration of patients were recorded. Patients with a history of other vascular diseases such as hypertension, diabetes mellitus, peripheral artery disease, and acute relapses were excluded.ResultsSixty-nine participants were included. The mean age of the study population was 35.8 ± 7.1 years. Right CIMT was significantly greater in the patient population (P < 0.001). Spearman's correlation coefficient between age and right CIMT was r = 0.41, P = 0.01. When we compared the Hs-CRP with a cut-off value of ≤ 3, the right, left, and mean CIMT levels were not statistically significant (P = 0.17; P = 0.22; P = 0.15). The mean serum vitamin D levels were higher in the patient group and this was statistically significant (P < 0.001). The statistically significant factors identified with univariate analysis with P < 0.2 were further entered into multivariate modelling.ConclusionCIMT seems to be affected in patients with MS by means of the disease itself and age. Thus, CIMT might reflect the predisposition to subclinical atherosclerosis more than Hs-CRP. Further investigation in a large MS population is still needed.     

Importance of acylcarnitine profile analysis for disorders of lipid metabolism in adolescent patients with recurrent rhabdomyolysis: Report of two cases

Metabolic myopathies due to disorders of lipid metabolism are a heterogeneous group of diseases. Newborns may present with hypotonia and convulsions, while progressive proximal muscle weakness or recurrent episodes of muscle weakness accompanied by rhabdomyolysis/myoglobinuria may be seen in older ages. There is little knowledge on detection of disorders of lipid metabolism by acylcarnitine profile (ACP) analysis by tandem mass spectrometry outside the neonatal period particularly in cases with recurrent rhabdomyolysis first presenting in adolescence and adulthood. Two adolescent female cases presented with episodes of rhabdomyolysis and muscle weakness. A 13-year-old patient had five episodes of rhabdomyolysis triggered by infections. Tandem mass spectrometry was normal. A 16-year-old female patient was hospitalized eight times due to recurrent rhabdomyolysis. Increased levels of C14:2, C14:1, and C14 were determined in tandem mass spectrometry. Final diagnoses were carnitine palmitoyltransferase II (CPT II) deficiency and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Increased serum levels of long-chain acylcarnitine can guide to the diagnosis of lipid metabolism disorders. Serum ACP should be performed before enzyme assay and genetic studies.     

Deep brain stimulation for Holmes’ tremor related to a thalamic abscess

BACKGROUND: Medical treatment is usually ineffective for Holmes' tremor, and surgery is the treatment of choice for many patients. Here we report the case of a 14-year-old girl who developed Holmes' tremor related to a thalamic abscess and was successfully treated with thalamic deep brain stimulation. CASE REPORT: The patient presented with left hemiparesis and headache and was hospitalized. Investigation revealed a thalamic abscess in the left cerebral hemisphere. The abscess was drained via stereotactic surgery and a course of antibiotic treatment was completed. Four months after treatment, the patient developed Holmes' tremor in her left upper extremity. When attempts at medical treatment with levodopa, clonazepam, and trihexyphenidyl all failed, an implant was placed and deep brain stimulation of the ventral intermediate nucleus of the thalamus was initiated. During 2.5 years of follow-up, her tremor diminished by 90%. CONCLUSION: This case demonstrates that medically resistant Holmes' tremor related to a thalamic lesion can be successfully treated with thalamic deep brain stimulation.     

Clinical utility of dorsal sural nerve conduction studies in healthy and diabetic children.

OBJECTIVE: Monitoring of the dorsal sural sensory nerve action potential (SNAP) is a sensitive method for detection of peripheral neuropathies. We tried to determine the normal dorsal sural nerve conduction values of the childhood population and assessed the clinical utility of this method in diabetic children who have no clinical sign of peripheral neuropathy. METHODS: In the study, 36 healthy and 27 diabetic children were included. In all subjects peripheral motor and sensory nerve studies were performed on the upper and lower limbs including dorsal sural nerve conduction studies. RESULTS: The dorsal sural SNAP mean amplitude was 8.24+/-3.08 microV, mean latency was 2.47+/-0.48 ms, mean sensory conduction velocity was 41.63+/-5.43 m/s in healthy children. Dorsal sural SNAPs were absent bilaterally in one diabetic patient. In the other 26 diabetic patients, the mean dorsal sural nerve distal latency was longer (2.93+/-0.63 ms, P = 0.004), mean SCV was slower than in healthy subjects (36.68+/-7.66 m/s, P = 0.005). However, dorsal sural nerve amplitude was not different between the groups. A dorsal sural nerve latency of more than 2.9 ms had a sensitivity of 50% and a specificity of 75%. A dorsal sural nerve velocity of less than 36 m/s had a sensitivity of 54% and a specificity of 92%. CONCLUSIONS: We designated the reference values of the dorsal sural nerve in healthy children. In addition, our findings suggest that dorsal sural nerve conduction studies may have value to determine neuropathy in the early stages in children with diabetes. SIGNIFICANCE: The dorsal sural nerve conduction studies in diabetic children may have value to determine the neuropathy in its early stages.     

Effects of etanercept on urine neopterin levels in patients with psoriasis in a controlled, open-label study

Neopterin is an immunological marker of cellular immune activation. Etanercept is a tumor necrosis factor-α (TNF-α) antagonist that decreases excessive levels of TNF-α associated with inflammatory disease down to physiological levels. The objective of this study was to investigate urine neopterin levels in psoriatic patients treated with etanercept, to study the effect of etanercept as a TNF-α blocker on urine neopterin levels. Urine neopterin levels and urine neopterin/creatinine ratios were measured by high-performance liquid chromatography in 22 patients with psoriasis before and after treatment with etanercept. Results were compared with a group of 20 healthy volunteers, and 20 patients with inflammatory skin diseases as control groups. Urine neopterin levels, neopterin/creatinine ratios and Psoriasis Area and Severity Index (PASI) scores were evaluated at baseline, and the 12th and 24th week after treatment. Urine neopterin levels were significantly elevated in the psoriatic group compared with control and inflammatory skin diseases groups ( P  < 0.05). Urine neopterin levels were significantly reduced after etanercept treatment. Statistically we did not find any correlation between neopterin levels and PASI scores. Our findings indicate that urine neopterin concentrations may reflect the disease activity in psoriasis, and may be used as a marker for monitoring disease activity and response to treatment with etanercept in psoriatic patients.     

The association between symptoms of sexual dysfunction and age at onset in Parkinson’s disease

Objective

Age at onset in Parkinson’s disease (PD) seems to be related nonmotor symptoms. In this study we investigated the effect of the age at onset on symptoms of sexual dysfunction (SSD) in patients with PD.

Methods

This prospective study comprised 22 consecutive outpatients with early onset PD (EOPD—onset of the disease before 55 years), and 66 outpatients with late onset PD (LOPD—onset of PD over 55 years). They were all recruited from the Department of Movement Disorders, Clinic of Neurology. The diagnosis was established according to the UK PD Brain Bank Criteria by a movement disorders specialist. The Unified PD Rating Scale (UPDRS) motor was used to assess motor disability and Hoehn and Yahr (H&Y) stage was used to establish disease severity. The sexual functions of the patients were rated by applying the Arizona Sexual Experiences Scale (ASEX).

Results

Thirteen EOPD patients (59.09 %) and 53 of the LOPD patients (80.3 %) (p 0.047) reported dissatisfaction with at least one item of ASEX. There were no differences between H&Y stages (p 0.205) UPDRS total (p 0.267) and motor scores (p 0.100) between groups. LOPD patients had significantly higher ASEX scores than EOPD patients (p 0.001).

Interpretation

Sexual dysfunciton occurs more frequently and more severely in LOPD than EOPD patients. PD patients with different ages at onset clinically present differently in terms of SSD.

     

Is the Cell Death in Mesial Temporal Sclerosis Apoptotic?

PURPOSE: Mesial temporal sclerosis (MTS) is characterized by neuronal loss in the hippocampus. Studies on experimental models and patients with intractable epilepsy suggest that apoptosis may be involved in neuronal death induced by recurrent seizures. METHODS: We searched evidence for apoptotic cell death in temporal lobes resected from drug-resistant epilepsy patients with MTS by using the terminal deoxynucleotidyl transferase (TdT) and digoxigenin-11-dUTP (TUNEL) method and immunohistochemistry for Bcl-2, Bax, and caspase-cleaved actin fragment, fractin. The temporal lobe specimens were obtained from 15 patients (six women and nine men; mean age, 29 +/- 8 years). RESULTS: Unlike that in normal adult brain, we observed Bcl-2 immunoreactivity in some of the remaining neurons dispersed throughout the hippocampus proper as well as in most of the reactive astroglia. Bax immunopositivity was increased in almost all neurons. Fractin immunostaining, an indicator of caspase activity, was detected in approximately 10% of these neurons. Despite increased Bax expression and activation of caspases, we could not find evidence for DNA fragmentation by TUNEL staining. We also could not detect typical apoptotic changes in nuclear morphology by Hoechst-33258 or hematoxylin counterstaining. CONCLUSIONS: These data suggest that either apoptosis is not involved in cell loss in MTS, or a very slow rate of cell demise may have precluded detecting TUNEL-positive neurons dying through apoptosis. Increased Bax expression and activation of caspases support the latter possibility.