Atypical Aicardi-Goutieres syndrome: is the WRN locus a modifier?

We describe a 28-year-old Turkish man with consanguineous parents who presented with an aged appearance with prematurely gray hair and scleroderma-like skin, spastic paraplegia, and apparent disability. The proband and each of his parents were heterozygous for a mutation in WRN, which could not explain his symptoms. Exome sequencing of the proband's blood DNA showed a homozygous c.626-1G > C mutation in intron 5 of the SAMHD1 gene, which encodes a triphosphohydrolase involved in the regulation of intracellular dNTP pools and which is mutated in Aicardi-Goutieres syndrome. The RNA studies confirmed aberrant splicing of exon 6, and family studies showed that both parents are heterozygous for this mutation. We conclude that mutations in SAMHD1 - in addition to causing an early-onset form of encephalopathy in Aicardi-Goutieres syndrome - may present with modest signs of accelerated aging similar to Werner syndrome. The extent to which heterozygosity at the WRN locus may modify the effect of biallelic SAMHD1 mutations is unknown. It is conceivable that synergistic effects of these two mutations might be responsible for the unusual phenotype.

Combined Central and Peripheral Demyelination in a Case With Sjogren Syndrome.

INTRODUCTION: Combined central and peripheral demyelination (CCPD) is a rare entity in which central and peripheral nervous system demyelination coexist. Herein, we present a patient with coexistence of Sjögren syndrome (SS) and CCPD. CASE REPORT: A 58-year-old female patient was admitted to our neurology clinic with paraparesis, difficulty walking, imbalance, and paresthesia. Neurological examination showed paraparesis, absence of lower extremity deep tendon reflex, sensory deficit at the T8 level, loss of deep sensory position, and vibration. Spinal magnetic resonance imaging revealed multiple focal T2-hyperintense and contrast-enhancing cord lesions. Fat-suppressed imaging disclosed T2 hyperintensity in lumbar nerve roots, diffuse linear enhancement of the cauda equina, and diffuse increased enhancement in lumbar nerve roots. Electrodiagnostic findings fulfilled the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy. Extensive laboratory workup excluded all possible pathologies. The Schirmer test detected positive in both eyes and minor salivary gland biopsy resulted in grade 3. These results were consistent with SS. The patient received intravenous methylprednisolone, azathioprine hydroxychloroquine. Approximately 2 years later, her complaints had completely disappeared, except for mild sensory complaints. CONCLUSION: It is unclear whether the association of central nervous system and peripheral nervous system demyelination and SS is a coincidence or a consequence. Our patient shows that patients with SS can have CCPD, and a significant clinical response can be obtained with early treatment. We hope that this unique case sheds light on the pathophysiology of CCPD.

Power spectral analysis of heart rate variability: normal values of subjects over 60 years old.

Power spectral analysis of heart rate variability (HRV) provides a non-invasive method of estimating cardiac autonomic nerve activity. It has been reported that HRV decreases with age. The purpose of this study was to assess the values of and determine the reliability of HRV in healthy older people. The study found lower and highly variable values of HRV. It was concluded that the reliability of HRV in older subjects might need to be reinvestigated and only normalized values of HF and LF might be useful. Larger study groups and different recording periods of HRV are needed.

Effects of different exercise modalities on ataxia in multiple sclerosis patients: a randomized controlled study.

PURPOSE: To investigate the effects of different exercise protocols on ataxia in patients with multiple sclerosis (MS). METHOD: A total of 42 MS patients, 17 male and 25 female (Expanded Disability Status Scale (EDSS): 3-5), were enrolled in this randomized controlled study. The patients were divided into three groups: a balance training (BT) group, a lumbar stabilization (LS) group and a task-oriented training (TT) group. All groups received balance training; additionally, the LS group received lumbar stabilization exercises, and the TT group received task-oriented training. The Berg Balance Scale (BBS), International Cooperative Ataxia Rating Scale (ICARS), Functional Reach Test (FRT), 2-Minute Walk Test (2MWT), Sensory Organization Test (SOT), and measurement of Somatosensory Evoked Potentials (SSEPs) were performed before and at the end of the 18 training sessions. RESULTS: The BBS, ICARS, FRT, 2MWT, and composite balance score of the SOT were improved in all groups. The ICARS kinetic function sub-score and the left limb cortical onset amplitudes of SSEPs were increased significantly in both the TT and the LS groups. The ICARS total score, composite balance score, and 2MWT were different between groups (p < 0.05). According to multiple comparison analyses of the ICARS total score and the composite balance score, the LS, and the TT group were different from the BT group (p < 0.005), while the LS and the TT groups improved similarly (p > 0.005). The 2MWT results were better for the LS group than the BT group, while the BT and the TT groups improved similarly. CONCLUSION: Balance training alone is not sufficient for rehabilitation of ataxic MS patients. A combination of lumbar stabilization exercises or task-oriented training increases the success of balance rehabilitation. Implications for rehabilitation Multiple sclerosis is a chronic inflammatory and autoimmune disease of central nervous system and ataxia is one of the most challenging symptoms of this disease. Different exercise modalities are commonly employed to control ataxic symptoms in MS patients. Lumbar stabilization exercises or task-oriented training should be considered as complementary approach to improve balance and coordination in ataxic multiple sclerosis patients.

Acute Disseminated Encephalomyelitis after Oral Therapy with Herbal Extracts: A Case Report.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disease of the central nervous system, commonly attributed to infections or vaccinations. Toxic or allergenic compounds can also trigger a response in the immune system and may cause demyelination. We present a case with ADEM after using oral herbal medications. CASE REPORT: A 25 year-old male developed bilateral central facial palsy and severe quadriparesis after taking herbal drugs (containing echinacea and many other herbal ingredients) for two weeks. He had used the extract to increase his potency and reproductivity. He had no past history of recent immunization or viral infection. The clinical findings, cerebrospinal fluid (CSF) analysis and brain magnetic resonance imaging (MRI) were compatible with ADEM. The neurological findings were improved after seven doses of pulse methylprednisolone treatment. To our knowledge, this is the third report in the literature that links herbal therapy and demyelinating disease. CONCLUSION: Most of the ADEM cases related to herbal therapy in the literature similarly used echinacea. It is our opinion that other ingredients of the herbal extract used by our case, besides echinacea, could have the potential to cause a trigger in the immune system. Further studies are needed to clarify the immunological effects of different kinds of herbal compounds, as well as the effects of different parts of the plants and the results of various dosages. Moreover, ingredients should also be tested for toxicity, adverse effects and drug interactions.

Brachial Diparesis due to Motor Neuronopathy as One of the Predominant Presenting Signs of Occult Small Cell Lung Carcinoma.

Sensory neuronopathy is a well-established presentation in paraneoplastic neurological syndromes that is mostly associated with small cell lung cancer and anti-Hu antibodies. Motor neuronopathy, on the other hand, is an extremely rare observation in this syndrome. A 56-year-old man presented with asymmetric brachial diparesis and sensory ataxia. Electrophysiological studies revealed sensory ganglionopathy and progressive anterior horn degeneration in cervical segments. Small cell lung carcinoma with associated anti-Hu antibodies was later diagnosed. The patient did not improve despite the administration of steroids and chemotherapy. Paraneoplastic syndromes may exceptionally present with a bilateral arm weakness. Cases accompanied by sensory ganglionopathy should therefore be promptly investigated for any underlying malignancy.

Normal values for single fiber EMG parameters of frontalis muscle in healthy subjects older than 70 years.

OBJECTIVE: Single fiber EMG (SFEMG) is a potent electrophysiological method to evaluate impaired neuromuscular transmission, and allows sensitive diagnosis of neuromuscular transmission abnormalities such as myasthenia gravis. The jitter and fiber density values are different for various muscles and age groups and the reference values increase with age. In this study, we evaluated the reference values of jitter and fiber density of frontalis muscle in healthy subjects older than 70 years. METHODS: We evaluated the jitter and fiber density of frontalis muscle in 32 healthy subjects. Twenty-two of them were between 70 and 79 years old (mean +/- SD, 73.9 +/- 1.7), and 10 of them were older than 80 years (mean +/- SD, 82.2 +/- 1.2). RESULTS: Normal limit of jitter (95% confidence limit) was calculated as 40.4 micros for healthy subjects between 70 and 79 years old and 43.7 micros for healthy subjects older than 80 years and normal limit of fiber density (95% confidence limit) were calculated as 1.90 for subjects between 70 and 79 years old and 2.14 for subjects older than 80 years. CONCLUSIONS: We designated the reference values of jitter and fiber density for frontalis muscle in healthy subjects older than 70 years. Our reference values may have value to diagnose neuromuscular transmission abnormalities in elderly patients. SIGNIFICANCE: SFEMG is sensitive for neuromuscular transmission abnormalities and it is important to know the reference values of frontalis muscle in healthy subjects older than 70 years.

Evoked potentials in children with Wilson's disease.

We assessed multimodal evoked potentials (EPs) in 13 children with newly diagnosed neurologically symptomatic Wilson's disease (WD) and in their first degree symptom-free relatives, consisting of seven presymptomatic and 15 asymptomatic siblings and 22 asymptomatic parents. EP abnormalities of at least one modality and one side stimulation were observed in 38.5% of patients, 42.9% of presymptomatic siblings, 21.4% of asymptomatic siblings and 18.2% of parents. Patients tended to have more prolonged central latencies of EPs. However, the left I-V interpeak brainstem auditory EP latency difference was the only one to reach at the statistical significance (P = 0.001). Abnormal VEP P100 latency was detected more frequently in presymptomatic siblings than those in asymptomatic ones (42.9% vs 7.1%, P = 0.049). In all relatives, other diagnostic tests including electroencephalography, electromyography and head magnetic resonance imaging (MRI) for subclinical nervous system involvement and Kayser-Fleischer rings examination yielded normal results. In pre/asymptomatic siblings, genetic and biochemical studies may aid to initiate treatment prior to the development of permanent tissue damage. Our results indicate that abnormal EPs may signal unique pathological finding in some subjects. Importantly, these abnormalities occur earlier than Kayser-Fleischer rings and MRI lesions. In early stages of WD, EP recordings may, therefore, be used to help decide on treatment initiation and treatment efficacy evaluation. Moreover, EP recordings can readily be added to family screening studies.

Erythropoietin against cisplatin-induced peripheral neurotoxicity in rats.

Cisplatin (CDDP) is a potent anticancer drug, and neurotoxicity is one of its most important dose-limiting toxicities. In this study we investigated the role of recombinant human erythropoietin (rhuEPO) for protection against CDDP-induced neurotoxicity. All experiments were conducted on female Wistar-albino rats. Animals were randomly assigned to three groups. Group A received only CDDP, group B received CDDP plus rhuEPO, and group C received only rhuEPO. Electroneurography (ENG) was done in the beginning and at the end of 7 wk, then the rats were sacrificed and the sciatic nerve was removed for histopathological examination. The mean initial latency was 2.7438 ms in group A, 2.4875 ms in group B, and 2.62 ms in group C. After 7 wk of treatment, the latency was 2.4938, 2.6313, and 2.3900 ms, respectively. The difference in latencies was not statistically significant. The amplitude of compound muscle action potential (CMAP) was 12.8125 mV, 14.3875 mV, and 14.5600 mV before the treatment and 8.4875, 12.8250, and, 13.0800 mV after treatment, respectively. Amplitude of CMAP was significantly greater in rhuEPO-treated groups (groups B and C) compared to cisplatin only Group A. The mean area of CMAP was 12.2625, 12.3500, and, 12.2800 mV s before the treatment and 5.7125, 10.6463, and 9.1600 mV s after the treatment, respectively. The area of CMAP was significantly larger in rhuEPO-treated groups. In histopathological studies thick, thin, and total number of nerve fibers were 4053, 5050, and 9103, in group A, 5100, 8231, and 13331, in group B, and 5264, 6010, and 11274, in group C respectively. In the microscopic examination active myelinization process was observed in rhuEPO-treated groups. We concluded that at the given dose and schedule CDDP-induced motor neuropathy and rhuEPO prevented this neuropathy by sparing the number of normal nerve fibers and by protecting the amplitude and area of CMAP. We concluded that rhuEPO may also play a role in active myelinization and it is an active agent in protection against CDDP-induced peripheral neuropathy, warranting further clinical studies.

Protective effect of amifostine against cisplatin-induced motor neuropathy in rat.

Cisplatin (CDDP) is a potent anticancer drug. Neurotoxicity is one of the most important dose-limiting toxicity of CDDP. We investigated the role of amifostine in the protection against CDDP-induced neurotoxicity especially on the motor nerves. All experiments were conducted on female Wistar albino rats. Animals were randomly assigned to two groups, each including six rats. Group A received CDDP plus amifostine and Group B received CDDP only. Electroneurography (ENG) was carried out in the beginning and at the end of 7 wk; then, the rats were sacrificed and the sciatic nerve was removed for histopathological examination. The mean initial latency was 2.4667 msn for group A and 2.44833 msn for group B. After 7 wk of treatment, the latency was 2.9167 for group A and 2.6333 for group B. The difference in latencies was not statistically significant. The amplitude was 11.7853 mV and 13.533 mV for groups A and B, respectively. After 7 wk of treatment, the amplitude was 9.400 mV and 9.000 mV, respectively. The decrease of amplitude in compound muscle action potential (CMAP) was 20% in the amifostine group and the decrease was 33% in the untreated group. The mean area of the CMAP in group A was 9.400 mVsn initially and 9.666 mVsn at the end of the treatment; there was a 0.3% increase despite CDDP treatment. In group B, the mean area of the CMAP was 13.816 mVsn initially and 11.857 mVsn at the end of the treatment; this corresponded to a statistically significant 14% decrease as a result of CDDP treatment. The ENG and histopathological studies showed that at the given dose and schedule CDDP-induced motor neuropathy and amifostine reduced this neuropathy both by protection of the amplitude and area of the CMAP in ENG studies and by sparing a larger number of nerve fibers.

Involvement of the central nervous system in Miller Fisher syndrome: a case report.

Miller Fisher syndrome (MFS) is characterised by ophthalmoplegia, ataxia and areflexia. Reports on cerebellar ataxia and supranuclear oculomotor derangement in MFS suggested an additional involvement of the central nervous system (CNS), resembling Bickerstaff's brainstem encephalitis (BBE). In the present report, a patient with a monophasic acute illness, early recovery and specific clinical-laboratory findings suggested both intrinsic brainstem and peripheral nerve disease (MFS and BBE). In pons and medulla oblangata, blurred to discrete T2-lesions were revealed by cranial MRI, while involvement of peripheral nerves was detected with EMG. The CSF showed no increase in protein or cell content, such as occurs in brainstem encephalitis.

Paroxysmal autonomic alterations mimicking epilepsy: a case report.

A 22-year-old male patient presented with paroxysmal hyperhidrosis, mydriasis, hypertension, and tachycardia. Cranial and cervical MRI revealed focal atrophy in the high order zone of the central autonomic network and syringomyelia. His physical and neurological examinations were unremarkable. Physiological testing included EEG, SPECT, serum/urine tests and autonomic testing. A poor response was achieved with the medical and interventional procedures employed. As the central autonomic network is an integral component of the internal regulation system of the brain, any lesion, no matter where in the network, may lead to paroxysmal autonomic alterations mimicking epilepsy (Published with videosequences).

Effects of exercise and electrical stimulation on lumbar stabilization in asymptomatic subjects: a comparative study.

BACKGROUND AND OBJECTIVES: Segmental stabilization training and electrical stimulation are used as a treatment for patients with low back pain. There is limited information on the efficacy of two interventions in the literature. In this study, the efficacy of the two interventions on the multifidus muscle activation and fatigue, segmental stabilization training and electrical stimulation, were examined and compared. MATERIAL AND METHODS: Our sample consists of 30 asymptomatic individuals, randomly assigned to one of three groups: the group that was given segmental stabilization training, the group that was given electrical stimulation and the control group that received no treatment. The muscle activity and fatigability of the multifidus were recorded by the surface electromyography before and after the intervention. RESULTS: No difference is detected for any of the multifidus muscle activation and fatigue characteristics either within or between groups. CONCLUSION: Both techniques did not improve multifidus activation capacity. An effort at submaximal and maximal level affects and increases the activity of multifidus.

In vivo application of poly-3-hydroxyoctanoate as peripheral nerve graft.

OBJECTIVE: This study aims to investigate the degree of biocompatibility and neuroregeneration of a polymer tube, poly-3-hydroxyoctanoate (PHO) in nerve gap repair. METHODS: Forty Wistar Albino male rats were randomized into two groups: autologous nerve gap repair group and PHO tube repair group. In each group, a 10-mm right sciatic nerve defect was created and reconstructed accordingly. Neuroregeneration was studied by sciatic function index (SFI), electromyography, and immunohistochemical studies on Days 7, 21, 45 and 60 of implantation. Biocompatibility was analyzed by the capsule formation around the conduit. Biodegradation was analyzed by the molecular weight loss in vivo. RESULTS: Electrophysiological and histomorphometric assessments demonstrated neuroregeneration in both groups over time. In the experimental group, a straight alignment of the Schwann cells parallel to the axons was detected. However, autologous nerve graft seems to have a superior neuroregeneration compared to PHO grafts. Minor biodegradation was observed in PHO conduit at the end of 60 d. CONCLUSIONS: Although neuroregeneration is detected in PHO grafts with minor degradation in 60 d, autologous nerve graft is found to be superior in axonal regeneration compared to PHO nerve tube grafts. PHO conduits were found to create minor inflammatory reaction in vivo, resulting in good soft tissue response.

Diagnostic value of double-step nerve stimulation test in patients with myasthenia gravis.

OBJECTIVE: Double-step nerve stimulation test (DSST) is a repetitive nerve stimulation (RNS) technique that is performed under exercise and ischemic conditions. We tested the diagnostic significance of DSST at a distal muscle in 17 control subjects and 10 myasthenic patients who had normal conventional RNS test. METHODS: Myasthenia gravis was diagnosed by SFEMG test and acetylcholine receptor antibody titers. During DSST decremental responses were noted. Sensitivity/specificity of DSST were evaluated by receiver operating characteristics (ROC) analysis and best variable in discrimination of myasthenic patients from control subjects with its optimal cutoff-point was selected. RESULTS: At a selected cutoff-point, sensitivity and specificity of DSST reached up to 100%. Also DSST response patterns, especially during the resolution of ischemia, showed significant differences in MG patients. There was a delayed recovery in the ischemia-exercise aggravated decremental response after the resolution of ischemia in the patients when compared with rapid recovery in controls. CONCLUSIONS: By using ROC derived cutoff-points, DSST could accurately discriminate MG patients from control subjects. Quantitative results of our study are limited by small series of patients and can vary with larger series. However we think that the difference between the decremental response patterns of patients and controls is a valuable finding. SIGNIFICANCE: DSST can be a sensitive, specific and non-invasive choice in the patients who have high suspicion for MG but normal conventional RNS.

Assessment of the short-term effect of antispastic positioning on spasticity.

BACKGROUND: This study was performed in order to investigate the effect of antispastic positioning on spasticity by using different assessment methods. METHODS: A total of 16 patients (11 males [68.75%] and five females [31.25%]), diagnosed as spastic diplegic and referred to the School of Physical Therapy and Rehabilitation, Paediatric Rehabilitation Unit for treatment, were included in this study. The mean age of patients was 6.43 +/- 1.99 years (range, 4-13 years). Passive dorsi-flexion movement was measured by using goniometer and intensity of spasticity was determined by using Modified Ashworth Scale (MAS) and electromyography. For the objective measurement of severity of spasticity, Hoffman reflex (H) and Hoffman reflex/motor response (H/M) ratios were used. Children were placed in an antispastic position for 20 min. The patient was placed in a sitting position, by a physiotherapist, with hips abducted at a 45 degrees angle and externally rotated, knees extended, and ankles placed in a neutral position. RESULTS: The decrease in H responses, H/M ratios, MAS values and the increase in goniometric measurement values were found statistically significant after antispastic positioning (P < 0.05). CONCLUSION: Our study supports that antispastic positioning can be used with neurodevelopmental treatment approaches when it is required. Antispastic positioning may help exercises to be performed more easily, and also has importance in a home exercise program to prevent muscle contractures and joint limitation in children with long-term spastic diplegia.

Impact of epineurial excision of the distal recipient nerve in terminolateral neurorrhaphy.

Different surgical modifications were studied to improve success in terminolateral neurorrhaphy. The authors evaluated the efficacy of distal epineurial excision of the recipient nerve stump. Forty male Wistar rats were evaluated in four groups. The right hind limbs of the animals were used as experimental limbs and the left hind limbs as control limbs. The peroneal nerve was transected at a level 1 cm above the bifurcation of the tibial nerve. The proximal stump of the peroneal nerve was covered with gluteus maximus muscle fibers in all groups. In Group 1, the distal peroneal nerve was not processed and was left in the operative field. In Group 2, the distal peroneal nerve stump was sutured to an epineurial window on the tibial nerve by epineurial neurorrhaphy. In Group 3, the distal stump of the peroneal nerve was buried in the tibial nerve without epineurial resection, and in Group 4 with a 1-mm epineurial excision. Walking track analyses, electromyographic studies, and histomorphometric analyses were performed after a 3-month follow-up period. Statistical analysis was done with ANOVA and Tukey tests. No important donor-nerve injury was detected. Axonal regeneration and functional results were better in Group 4 compared to Groups 2 and 3. An increased donor and recipient nerve contact surface area with the excision of the epineurium from the distal peroneal nerve stump (Group 4) might provide superior results with longer follow-up periods.