Ayşegül Gündüz

The interleukin 1 alpha, interleukin 1 beta, interleukin 6 and alpha-2-macroglobulin serum levels in patients with early or late onset Alzheimer's disease, mild cognitive impairment or Parkinson's disease

Alzheimers disease (EOAD, LOAD), mild cognitive impairment (MCI), Parkinsons disease (PD) and healthy controls were included to determine the serum interleukin-1s (IL-1α, IL-1β), IL-6 and alpha-2-macroglobulin (α2M) levels using ELISA. IL-6 might be a significant contributor to the inflammatory response in LOAD. The MCI data indicate that IL-1s, α2M and BDNF are somehow related, and this relationship might allow MCI patients to be more similar to the healthy controls. A correlation analysis of multiple biomarkers in different neurodegenerative disorders might be more useful than determining the levels of a single cytokine in a single disorder.

Functional deficiencies of sulfite oxidase: Differential diagnoses in neonates presenting with intractable seizures and cystic encephalomalacia

Sulfite oxidase is a mitochondrial enzyme encoded by the SUOX gene and essential for the detoxification of sulfite which results mainly from the catabolism of sulfur-containing amino acids. Decreased activity of this enzyme can either be due to mutations in the SUOX gene or secondary to defects in the synthesis of its cofactor, the molybdenum cofactor. Defects in the synthesis of the molybdenum cofactor are caused by mutations in one of the genes MOCS1, MOCS2, MOCS3 and GEPH and result in combined deficiencies of the enzymes sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase. Although present in many ethnic groups, isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are rare inborn errors of metabolism, which makes awareness of key clinical and laboratory features of affected individuals crucial for early diagnosis. We report clinical, radiologic, biochemical and genetic data on a Brazilian and on a Turkish child with sulfite oxidase deficiency due to the isolated defect and impaired synthesis of the molybdenum cofactor, respectively. Both patients presented with early onset seizures and neurological deterioration. They showed no sulfite oxidase activity in fibroblasts and were homozygous for the mutations c.1136A>G in the SUOX gene and c.667insCGA in the MOCS1 gene, respectively. Widely available routine laboratory tests such as assessment of total homocysteine and uric acid are indicated in children with a clinical presentation resembling that of hypoxic ischemic encephalopathy and may help in obtaining a tentative diagnosis locally, which requires confirmation by specialized laboratories.

Peripheral neuropathy in patients with diabetic foot ulcers: Clinical and nerve conduction study

OBJECTIVES Diabetic foot lesions develop predominantly in male patients and sensory neuropathy is the most frequent type of neuropathy associated with these lesions. The aim of this study was to analyze the clinical and electrophysiological features in a cohort of patients with diabetic foot. RESEARCH DESIGN AND METHODS The recordings of 318 consecutive diabetic patients (127 women and 191 men) with an ongoing or healed foot ulcer who had been referred for electrophysiological consultation were evaluated retrospectively. RESULTS 60.1% of our cohort were male. Loss of deep sensation and deep tendon reflex abnormalities were the most common neurological findings. Negative sensory symptoms (63.7% vs 40.8%, p<0.01) and neuropathic pain (38.5% vs 18.3%, p<0.01) were more frequent in females, whereas atrophy was more frequent in male patients (22.8% vs 46%, p<0.01). Motor nerve conduction abnormalities and ulnar nerve involvement was more frequent and severe in males. Abnormal electrophysiological findings were mild in 70 patients (female 42, 60%). In this group, hemiplegia, peripheral arterial disease, multiple bone fractures, end stage renal failure, recent pulmonary tuberculosis and dementia accompanied mild polyneuropathy. Thirty patients had shown prominent decrease in nerve conduction velocity which indicated severe demyelination. Among these 30 patients, 6 male subjects had clinical features similar to that of chronic inflammatory demyelinating polyneuropathy. CONCLUSIONS Our results indicate that male gender, motor neuropathy and mononeuropathies, especially ulnar neuropathy is associated with the development of DF among our patients with DF. Patients with diabetes mellitus have a predisposition to develop chronic inflammatory demyelinating polyneuropathy and this may also facilitate formation of diabetic foot. History of hemiplegia, dementia and trauma are permissive risk factors for diabetic foot in the presence of mild polyneuropathy.

Novel NDE1 homozygous mutation resulting in microhydranencephaly and not microlyssencephaly.

Lissencephaly is characterized by deficient cortical lamination. Recently homozygous NDE1 mutations were reported in three kindred afflicted with extreme microcephaly with lissencephaly or microlissencephaly. Another severe developmental defect that involves the brain is microhydranencephaly which manifests with microcephaly, motor and mental retardation and brain malformations that include gross dilation of the ventricles with complete absence of the cerebral hemispheres or severe delay in their development. In the three related patients with microhydranencephaly that we had reported previously, we identified a homozygous deletion that encompasses NDE1 exon 2 containing the initiation codon. The mutation is predicted to result in a null allele. Herein we compare the clinical phenotypes of our research patients to those reported as microlissencephaly. The clinical findings in our patients having the fourth NDE1 mutation reported so far widen the spectrum of brain malformations resulting from mutations in NDE1.

Outcomes in spasticity after repetitive transcranial magnetic and transcranial direct current stimulations

Non-invasive brain stimulations mainly consist of repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Repetitive transcranial magnetic stimulation exhibits satisfactory outcomes in improving multiple sclerosis, stroke, spinal cord injury and cerebral palsy-induced spasticity. By contrast, transcranial direct current stimulation has only been studied in post-stroke spasticity. To better validate the efficacy of non-invasive brain stimulations in improving the spasticity post-stroke, more prospective cohort studies involving large sample sizes are needed.

Cırcadıan changes ın cortıcal excıtabılıty ın restless legs syndrome

Various investigations have revealed a widespread and somewhat controversial pattern of cerebral, cerebellar and brainstem involvement in the pathophysiology of restless legs syndrome (RLS). However, several studies which investigated functional or structural aspects indicated cortical involvement in RLS. In this study, we aimed to analyze circadian changes of cortical excitability in idiopathic RLS patients by means of transcranial magnetic stimulation (TMS). Eleven idiopathic RLS patients and eight healthy age and sex matched subjects were investigated using single-pulse TMS and motor nerve conduction studies during early afternoon when there were no symptoms and late at night (22:00-23:00) when the symptoms reappeared. Central motor conduction time, latencies and amplitudes of scalp and cervical motor evoked potentials, resting and active motor thresholds, and cortical silent period were measured. Measured parameters were similar between RLS patients and healthy subjects during the daytime. At night, cortical silent periods tended to shorten, and motor thresholds tended to decrease in the RLS group, whereas in controls they tended to increase. At night, active motor-threshold measurements were significantly lower in the RLS group (28.5 ± 6.2% vs 40.4 ± 8.4%, p=0.006). Therefore, we propose that in patients with RLS, conduction along the motor corticospinal axons is normal, with the possible loss of subcortical inhibition at nighttime.

Can spontaneous intracranial hypotension cause venous sinus thrombosis

Sir, We present a 45-year-old man who had severe postural headache and high blood pressure. Postural headache had started 6 days previously and had lost postural feature in two days. Cranial magnetic resonance imaging (MRI) showed dural thickening, subdural effusion and superior sagittal sinus thrombosis. We observed diffuse

Hemimasticatory spasm following pontine infarction

age by growth charts. While in Iran, she was noted to have scoliosis and an MRI of the thoracic spine revealed an intramedullary, isointense, hetereogeneous, enhancing mass extending from the second thoracic level to the tenth thoracic level. An attempt at resection of the spinal mass and correction of the scoliosis was not successful but the biopsy specimen revealed a ganglioglioma. Since the surgery, the scoliosis has become worse, requiring a back brace for support and her gait has deteriorated with a right foot drop. Tumor size has been stable since the initial diagnosis. Radiation therapy was recommended but the family refused. The undulating abdominal movements ceaselessly continue. The documented thoracic intramedullary spinal tumor and the localized abdominal movements prompt us to suggest a direct clinical–anatomic correlation for this patient’s unusual movement disorder.

Auditory startle reflex and startle reflex to somatosensory inputs in generalized dystonia

OBJECTIVE Startle reflex is a generalized defense reaction after unexpected auditory, visual, or tactile stimuli. Auditory startle reflex (ASR) and startle reflex to somatosensory inputs (SSS) have never been studied in generalized dystonia. Here, we aimed to study the characteristics and changes of ASR and SSS in this group. METHODS We have examined ASR and SSS in patients with generalized dystonia (n=11) and healthy subjects (n=25) under the same conditions. ASRs and SSSs were recorded over the orbicularis oculi (O.oc), sternocleidomastoid, biceps brachii (BB), and abductor pollicis brevis (APB) muscles after bilateral auditory stimulation and unilateral median nerve electrical stimulation at the wrist, respectively. RESULTS Both ASR and SSS showed the same sequence of muscle activation in both groups. However, the presence rates over the APB and BB muscles after both modalities of stimuli were significantly higher in the generalized dystonia group. ASR did not habituate in the dystonia group. CONCLUSIONS Both ASR and SSS are disinhibited, and both show a similar sequence of muscle recruitment in generalized dystonia. SIGNIFICANCE Higher probabilities over caudal muscles probably depend on the higher excitability of motor neurons secondary to central modulation.

FBXO7–R498X mutation: Phenotypic variability from chorea to early onset parkinsonism within a family

OBJECTIVE FBXO7 mutations (PARK 15), first reported in 2008, are among the monogenic causes of early-onset parkinsonism. Classically, PARK 15 was suggested to correspond to previously described pallido-pyramidal syndrome. Here, we report clinical and genetic findings in a unique family of Kurdish origin with an FBXO7 mutation and presenting with diverse clinical phenotypes. METHODS The family consisted of 14 members (12 offspring) of whom three were affected. Two of these three siblings were examined in our clinic. DNA samples from the index case and his elder sister were subjected to homozygosity mapping and exomic sequencing. RESULTS The index case had progressive speech problems, severe apathy, chorea, and tics at presentation and developed very mild parkinsonism and postural instability after 3 years. His sister had young-onset asymmetric tremor-dominant parkinsonism with some atypical features, such as early development of postural instability, tics, and tachyphemic speech. She died of an akinetic-rigid condition and had not developed chorea. A homozygous R498X mutation was found in both patients (NM_012179; chr22:31,224,440). This result was further confirmed by Sanger sequencing in both patients, their consanguineous parents, and their maternal grandfather; the latter three were found to be heterozygous for the mutation (c.C1492T; p.R498X). CONCLUSIONS The family presented here broadens the clinical spectrum of parkinsonism to include tics and chorea, in addition to the parkinsonian-pyramidal phenotype, in connection with FBXO7 mutations and points to an intrafamilial phenotypic variation.