Çağrı Mesut Temuçin

Medial plantar and dorsal sural nerve conduction studies increase the sensitivity in the detection of neuropathy in diabetic patients

OBJECTIVE Clinical utility of nerve conduction studies (NCS) of the medial plantar and dorsal sural nerves in the early detection of polyneuropathy have already been shown separately. However, at present, there is no data about the combined assessment of these two nerves in distal sensory neuropathy. In the present study, we aimed to evaluate the medial plantar and dorsal sural NCS in a group of diabetic patients with distal sensory neuropathy (DSN) and in healthy controls. METHODS Thirty healthy and 30 diabetic adult patients were included. In all subjects, peripheral motor and sensory NCS were performed bilaterally with surface electrodes on the lower limbs including medial plantar and dorsal sural nerves. In addition, motor and sensory nerves were studied unilaterally on the upper limb. RESULTS In all patients, nerve action potential (NAP) amplitudes of sural and superficial peroneal nerves were within normal ranges, but in the patient group mean value was significantly lower than in the controls. Among clinically defined 30 DSN patients, medial plantar NAP amplitude was abnormal in 18 (60%) and dorsal sural nerve amplitude was abnormal in 13 (40%) of the patients bilaterally. Additionally, the onset NCV of the dorsal sural nerve was significantly slower in patients than controls (P=0.038). Evaluation of both of these nerves increased the sensitivity up to 70% in the detection of neuropathy. CONCLUSIONS Bilateral NCS assessment of both of the medial plantar and dorsal sural nerves together increases the rate of diagnosis of diabetic distal sensory neuropathy compared to assessment of either of these nerves. SIGNIFICANCE Assessment of medial plantar in addition to dorsal sural NCS together increases the sensitivity in the detection of neuropathy and allows earlier diagnosis, especially when routine NCS are normal.

Short latency afferent inhibition in Parkinson's disease patients with dementia†

Cortical cholinergic deficiency occurs in Parkinsons disease (PD) and is more severe in PD dementia (PDD). Short‐latency afferent inhibition (SAI) can be used as an in vivo test for the evaluation of the cholinergic circuit in the cerebral motor cortex.

Identification of a Novel Twinkle Mutation in a Family With Infantile Onset Spinocerebellar Ataxia by Whole Exome Sequencing

Whole exome sequencing combined with homozygosity mapping comprises a genetic diagnostic tool to identify genetic defects in families with multiple affected members, compatible with presumed autosomal recessively inherited neurometabolic/neurogenetic disease. These tools were applied to a family with two individuals manifesting ataxia, associated with peripheral sensory neuropathy, athetosis, seizures, deafness, and ophthalmoplegia. A novel homozygous missense mutation c.1366C>G (L456V) in C10orf2 (the Twinkle gene) was identified, confirming infantile onset spinocerebellar ataxia in the probands. Signs in infantile onset spinocerebellar ataxia follow a fairly distinct pattern, affecting early development, followed by ataxia and loss of skills. However, this very rare disease was previously reported only in Finland. We suggest that infantile onset spinocerebellar ataxia should be more frequently considered in the differential diagnosis of neurometabolic diseases in childhood. Next-generation sequencing and its use along with homozygosity mapping offer highly promising techniques for molecular diagnosis, especially in small families affected with very rare neurometabolic disorders such as infantile onset spinocerebellar ataxia.

Spontaneous unilateral accessory nerve palsy: a case report and review of the literature

Isolated spinal accessory nerve (SAN) palsy is a well-recognized complication of surgical prodecures in the posterior triangle of the neck. Various rare etiological factors were also described. Whatever the etiology, the typical clinical features of SAN palsy can be listed as atrophy/weakness of the trapezius muscle and moderate winging of the scapula. It is imperative to promptly diagnose this condition in the early stage to avoid long-term impairment and to have a better functional outcome. Herein, we present a patient with a diagnosis of spontaneous spinal accessory nerve palsy, which was rarely reported in the relevant literature.

Early-onset chronic axonal neuropathy, strokes, and hemolysis: Inherited CD59 deficiency

Objective: To identify the underlying etiology of 3 patients in a multiplex family with strokes, chronic immune-mediated peripheral neuropathy, and hemolysis. All had onset in infancy. Methods: We performed genome-wide linkage analysis followed by whole exome sequencing (WES) in the proband, Sanger sequencing, and segregation analysis of putative mutations. In addition, we conducted flow cytometry studies to assess CD59 expression. Results: In a 2-generation–3-affected family with early-onset immune-mediated axonal neuropathy, cerebrovascular event both in the anterior and posterior circulation, and chronic Coombs-negative hemolysis, we detected CD59 deleterious mutation as the underlying cause. Linkage analysis and homozygosity mapping using single nucleotide polymorphism (SNP) microarrays in the family followed by WES in one index case allowed identification of a homozygous missense mutation in the CD59 gene (c.A146T:p.Asp49Val). Sanger sequencing validated the mutation, showing cosegregation with the disease phenotype. Flow cytometry using blood cells in the 3 patients showed a lack of CD59 expression at the cell membrane compared to control and CD55 labeling. Conclusion: We added to the knowledge base about inherited CD59 deficiency.

Measurement of motor root conduction time at the early stage of Guillain–Barre syndrome

Background and purpose:  As they are mainly performed at distal nerve parts, routine electrophysiological examinations can fail to detect the abnormalities at the early stage of Guillain–Barre syndrome (GBS) because of predominant involvement of proximal nerve segments. Measurements focused on proximal conduction can provide additional findings. We investigated the diagnostic significance of motor root conduction time (MRCT) at the early stage of GBS.

Recessive PIEZO2 stop mutation causes distal arthrogryposis with distal muscle weakness, scoliosis and proprioception defects

The genetic work-up of arthrogryposis is challenging due to the diverse clinical and molecular etiologies. We report a-183/12-year-old boy, from a 2nd degree consanguineous family, who presented at 36/12 years with hypotonia, distal laxity, contractures, feeding difficulties at birth. He required surgery for progressive scoliosis at 16 years of age, and walked independently since then with an unstable gait and coordination defects. His latest examination at 18 years of age revealed a proprioceptive defect and loss-of-joint position sense in the upper limbs. Somatosensory evoked potentials supported bilateral involvement of dorsal column-medial lemniscal sensory pathways and nerve conduction studies revealed a mild axonal neuropathy. Muscle biopsy showed myopathic changes with neonatal myosin expression. Mendeliome sequencing led to the discovery of a recessive stop mutation in piezo-type mechanosensitive ion channel component 2 (PIEZO2, NM_022068, c.1384C>T, p.R462*). PIEZO2 is a nonselective cation channel, expressed in sensory endings of proprioceptors innervating muscle spindles and Golgi tendon organs. Dominant PIEZO2 mutations were described in patients with distal arthrogryposis type 5 and Marden–Walker syndrome. Sensory ataxia and proprioception defect with dorsal column involvement together with arthrogryposis, myopathy, scoliosis and progressive respiratory failure may represent a distinct clinical phenotype, and indicate recessive mutations in PIEZO2.

The effect of poly(3-hydroxybutyrate-co-3- hydroxyhexanoate) (PHBHHx) and human mesenchymal stem cell (hMSC) on axonal regeneration in experimental sciatic nerve damage

This study is designed to evaluate the treatment effect of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and human mesenchymal stem cells (hMSC) on axonal regeneration in experimental rat sciatic nerve damage, and compare the results of this modality with autologous nerve grafting. In Spraque–Dawley albino rats, 10-mm-long experimental nerve gaps were created. Three groups were constituted, the gap was repaired with autologous nerve graft (autograft group), PHBHHx nerve graft alone (PHBHHx alone group), and PHBHHx nerve graft with hMSCs inside (PHBHHx with hMSC group), respectively. The results were evaluated with functional recovery, electrophysiological evaluation, and histological evaluation either with light microscopy and transmission electron microscopy for axonal regeneration and myelin formation. In functional evaluation, autograft and PHBHHx with hMSC groups showed functional improvement with time, whereas PHBHHx alone group did not. Electrophysiological evaluation showed better results in autograft and PHBHHx with hMSC groups when compared to PHBHHx alone group. There was no statistical difference between autograft and PHBHHx with hMSC groups. Histological evaluation showed regenerated axons in each group. Autograft group was better than the others, and PHBHHx with hMSC group was better than PHBHHx alone group both for axonal regeneration and myelin formation. This study showed that the nerve grafts which were prepared from PHBHHx with oriented nanofiber three-dimensional surfaces aided to nerve regeneration, either used alone or with hMSC. PHBHHx provided better nerve regeneration when used with hMSCs inside than alone, and reached the same statistical treatment effect in functional evaluation and electrophysiological evaluation when compared to autografting.

Near‐nerve needle sensory and medial plantar nerve conduction studies in patients with small‐fiber sensory neuropathy

Background and purpose:  The aim of this prospective study was to show and compare the rate of large‐fiber involvement with near‐nerve needle sensory (NNNS) nerve conduction study (NCS) and with medial plantar NCS recorded with surface electrodes in a group of patients who had clinically pure small‐fiber sensory neuropathy (SFSN) with reduced intra‐epidermal nerve fiber density in skin biopsy and with normal routine NCS.

Tract-based spatial statistics of diffusion tensor imaging in hereditary spastic paraplegia with thin corpus callosum reveals widespread white matter changes.

PURPOSE We aimed to investigate white matter diffusivity abnormalities in hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) patients in relation with electrophysiological findings. MATERIALS AND METHODS Brain magnetic resonance imaging (MRI) and diffusion tensor imaging were performed on four HSP-TCC patients and 15 age-matched healthy subjects. Voxel-wise statistical analysis of fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity maps were carried out using tract-based spatial statistics, and significantly affected voxels were labeled using a human white matter atlas. Conventional nerve conduction studies, cortical and spinal-root motor evoked potentials, and somatosensory evoked potentials were examined in three patients. RESULTS On MRI, all patients had a thin corpus callosum with mild T2 hyperintensity in the periventricular white matter. Compared to control subjects, we detected widespread significant decreases in fractional anisotropy, and increases in axial diffusivity, radial diffusivity, and mean diffusivity in structures including in the corpus callosum, motor, and non-motor white matter tracts in HSP-TCC patients. Several different regions showed significant reduction in axial diffusivity. Electrophysiological studies revealed prolonged central motor conduction times and reduced cortical motor evoked potentials and somatosensory evoked potentials amplitudes in all patients. One patient had low sural sensory nerve action potential suggestive of axonal neuropathy. CONCLUSION Tract-based spatial statistics of diffusion tensor imaging revealed a more widespread involvement of white matter in HSP-TCC patients than has previously been detected by conventional MRI. This may explain the broad spectrum of electrophysiological and neurological abnormalities that complicate hereditary spastic paraplegia in these patients.