Zeliha Matur

Genotypic and phenotypic presentation of transthyretin-related familial amyloid polyneuropathy (TTR-FAP) in Turkey

Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is an autosomal dominant disorder caused by mutations of the transthyretin (TTR) gene. The mutant amyloidogenic transthyretin protein causes the systemic accumulation of amyloid fibrils that result in organ dysfunction. TTR-associated FAP is a progressive and fatal disease, if left untreated, and should be considered in the differential diagnosis of any person presenting with a progressive polyneuropathy, particularly with accompanying autonomic involvement. The clinical, electrophysiological, histopathological, and genetic characteristics of 17 patients from Turkey (5 female, 13 male) from nine families with polyneuropathy and mutations in TTR were evaluated. Sequence analysis of the TTR gene revealed five mutations (Val30Met, Glu89Gln, Gly53Glu, Glu54Gly and Gly47Glu). Mean age at disease onset was 40.4 ± 13.9 years (range 21-66 years). The most commonly reported initial complaint was paresthesia in the feet (asymmetric in three patients). Three patients (2 male) with the Glu89Gln mutation presented with carpal tunnel syndrome. Two patients with the Gly53Glu mutation showed episodes of dysarthria and hemiparesis, consistent with this genotype. Seven patients died during the period of follow-up as a result of systemic involvement. Our study suggests that a cohort of patients from Turkey with TTR-FAP exhibits clinical and genetic heterogeneity.

Analysis of the tremor in juvenile myoclonic epilepsy

PURPOSE We aimed to investigate juvenile myoclonic epilepsy (JME) patients complaining of tremor unrelated to valproate (VPA) treatment and evaluate if there were differences between JME patients with and without tremor and essential tremor (ET) patients to exclude comorbidity. METHODS Fifteen JME cases with the complaint of tremor, 14 JME patients without tremor, 14 patients with ET and 14 healthy subjects (HS) were included. Regularity, frequency and amplitude of the tremor and superimposed myoclonia were assessed by accelerometric analysis. Cortical SEPs evoked by the stimulation of the median nerve were recorded bilaterally. Clinical and neurophysiologic features were statistically compared between the groups. FINDINGS Amplitude of postural tremor of the left hand was significantly increased in the ET group compared to JME patients with tremor, but there were no differences regarding to frequency. Strikingly, there were superimposed irregular, low-amplitude inconstant myoclonic jerks located to distal part of the fingers in JME group with tremor. Initial frequency of myoclonic seizures was also significantly higher in this group compared to JME patients without tremor but this difference disappeared after treatment. The group of JME with tremor had the highest N20-P25 and P25-N35 amplitudes, followed by JME without tremor, ET and HS, respectively. CONCLUSION Tremulous hand movements in JME resembled ET, but their amplitude was lower and characterized with accompanying irregular myoclonic jerks. The presence of tremor in JME patients should be taken into consideration to create more homogeneous groups in genetic and pathophysiological studies of JME.

Genotypic and phenotypic presentation of Glu89Gln mutation in Turkey

Background Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is an autosomal dominant disorder caused by mutations of the transthyretin (TTR) gene. More than 100 different mutations of the transthyretin gene are identified worldwide, but still the first described Val30Met is the most common one. The mutant amyloidogenic transthyretin protein causes systemic accumulation of amyloid fibrils that results in organ dysfunction and death. TTR-associated FAP is a progressive and fatal disease if left untreated and should be considered in the differential diagnosis of any patient with a progressive polyneuropathy, especially with an accompanying autonomic involvement.

ID 309 – Clinical, electrophyisological and serological evaluation of patients with cramp-fasciculation syndrome

Objective Cramp-fasciculation syndrome (CFS) is a rare peripheral nerve hyperexcitability syndrome. There is little information on the clinical and serological profile of a CFS cohort followed by a single outpatient clinic. Method Clinical, electrophysiological and serological features of 6 CFS patients (5men/1woman, 27-61years-old) were investigated. Results All patients presented with cramps, fasciculations, muscle pain and autonomic symptoms, while two of them also reported numbness and burning sensation in the limbs which was reminiscent of neuropathic pain. Nerve conduction studies and RR interval variability tests revealed normal results. Sympathetic skin responses were increased in amplitude, and prolonged after-discharges were recorded from the foot muscles after tibial nerve stimulation in all the patients. Antibodies to voltage-gated potassium channel(VGKC)-complex proteins were found in 3patients, one of whom was also positive for contactin-associated protein-like2(CASPR2) antibody. Two patients with neuropathic pain displayed non-CASPR2 VGKC-complex antibodies. None of the patients had a malignancy. Five patients showed favorable response to carbamazepine or pregabalin treatment, whereas one VGKC-antibody positive patient was resistant to carbamazepine and immunosuppressant treatment. Conclusion Autonomic symptoms, neuropathic pain and VGKC-complex antibodies are commonly found in CFS patients. Key message VGKC-complex antibody positivity might be an indicator of neuropathic pain and resistance to treatment in CFS.

IMPULSIVITY IN ALZHEIMER’S DISEASE AS DETECTED BY D-CPT

Background: Genetic studies identified an association between Alzheimer’s disease (AD) and common polymorphisms in the MS4A and TREM loci, each containing cluster of homologous genes. Methods:We searched for rare coding variants in 15 genes mapped to these loci by next generation sequencing of a North American dataset (210 cases and 233 controls). Results:Analysis of the MS4A gene-cluster revealed loss-of-function variants in 6 controls and 3 cases. Investigation of the TREM gene-cluster detected known AD associated TREM2 substitutions (p.R47H, p.D87N and p.H157Y) affecting both TREM2 isoforms (NM_018965 and NM_001271821). We also identified two cases with novel TREM2 variants (p.L205P and p.G219C), which mapped only to the isoform NM_001271821. A p.S248R substitution in the homologous TREML2 gene was detected in 5 controls and 1 case suggesting a protective effect (pooled p-value 1⁄4 0.033). Conclusions:Our study advocates for the importance of mutation analysis of controls, particularly for GWAS loci containing SNPs with a minor allele frequency higher in controls versus cases (e.g. MS4A locus), to search for functional variants with a protective effect.

P420: EMG in pediatric population: was it worth it?

Question: Tarsal tunnel syndrome is the most frequent entrapment neuropathy of the posterior tibial nerve [1]. It may involve also its plantar and/or calcaneal branches [3]. It is a rare and frequently underdiagnosed condition leading to motor, sensory and autonomic complications affecting the sole. Early decompression in the symptomatic cases promotes good recovery [2]. Methods:We present the case of a 59-year-old female who was admitted to our Clinic with a 2-month-history of progressive weakness and burning of the right foot. The diagnosis of the symptomatic tarsal tunnel syndrome was made based on electrodiagnostic testing and magnetic resonance imaging of the right foot. Results: Electroneurography revealed a severe right tibial nerve injury in the tarsal tunnel. MRI showed a polycyclic cystic mass medially to the lower ankle joint distorting the swollen tibial nerve. The postoperative outcome was good. Conclusions: Tarsal tunnel syndrome can be easily overlooked due to the rarity and nonspecific symptoms of this pathology and a tumour in the tarsal tunnel is an exeptional cause [2]. Insightful electrodiagnostic testing can help identify the site of injury. When combined with imaging, it constitutes a proper therapeutic regimen. References: [1] Emeryk-Szajewska B, Niewiadomska-Wolska M. Neurofizjologia kliniczna. Medycyna Praktyczna, Krakow, 2008, pp. 229-231. [2] Ahmad M, Tsang K, Mackenney PJ, Adedapo AD. Tarsal tunnel syndrome: a literature review. Foot Ankle Surg 2012; 18: 148-152. [3] Binnie CD, Cooper R, Mauguiere F, Osselton JW, Prior PF, Tedman BM. Clinical Neurophysiology, Elsevier, 2004, pp. 136-138.