M. Nebuchennykh

Two novel SCN9A mutations causing insensitivity to pain.

The sensation of pain is important and there may be serious consequences if it is missing. Recently, the genetic basis for a channelopathy characterised by a congenital inability to experience pain has been described and channelopathy-associated insensitivity to pain has been proposed as a suitable name for this condition. Different mutations in the SCN9A gene causing loss of function of the voltage-gated sodium channel Nav1.7 have been reported in patients with this rare disease. Here we describe a woman with insensitivity to pain with two novel mutations in the SCN9A gene, coding for the Nav1.7 channel. We also discuss the finding of anosmia which apparently is a common feature in these patients.

Idiopathic polyneuropathy and impaired glucose metabolism in a Norwegian patient series.

Background and purpose:  North American studies have indicated a high prevalence of impaired glucose tolerance (IGT) in patients with sensory polyneuropathy. We searched for the occurrence of IGT in a Norwegian patient material with polyneuropathy.

Aspects of peripheral nerve involvement in patients with treated hypothyroidism

Background:  We studied involvement of large and small nerve fibres in patients with hypothyroidism and symptoms and signs of polyneuropathy.

190 TWO NOVEL SCN9A MUTATIONS CAUSING INSENSITIVITY TO PAIN

to “inflammatory soup”. In this study, we investigated the contribution of TRPV4 to thermal and mechanical hyperalgesia in wild type and TRPV4 knockout mice, following NGF administration. After acclimatisation, baseline measurements of the latency of withdrawal to radiant heat and 50% withdrawal threshold to repeated von Frey hair application to the plantar surface of the hind paws were made. The withdrawal threshold to pressure applied to the whole paw was also assessed. These measurements were repeated 1 hour and 24 hours after systemic administration of NGF (1mg/g, i.p.). No differences were seen between baseline measurements for wild type and knockout mice. Both wild type and knockout mice showed a significant decrease in the latency of withdrawal to heat stimuli and von Frey withdrawal thresholds at 1 hour and 24 hours following NGF injection, indicative of thermal and mechanical hypersensitivity. However, only wild type mice showed a reduced withdrawal threshold to paw pressure after NGF treatment. We conclude that TRPV4 sensitisation is involved in the increased sensitivity to paw pressure observed following NGF injection in mice.

Quantitative sensory testing in patients with polyneuropathy and healthy individuals

Aims –  Elderly individuals and patients with polyneuropathy often feel heat pain or burning sensation on quantitative sensory testing (QST) of warm perception distally in the lower limbs. We therefore studied heat pain threshold (HPT), warm perception threshold (WPT) and the difference between heat pain and warm perception thresholds in 48 patients with symptoms and signs of polyneuropathy matched according to age and gender with 48 healthy persons.

Charcot–Marie–Tooth disease type 4C in Norway: Clinical characteristics, mutation spectrum and minimum prevalence

Autosomal recessive Charcot-Marie-Tooth disease (CMT) is considered rare and phenotypic descriptions are scarce for the different subgroups. Mutations in the SH3TC2 gene, causing recessive demyelinating CMT type 4C have been found in several Norwegian CMT patients over the last years. We aimed to estimate a minimum prevalence and to study the genotypic and phenotypic variability of CMT4C in Norway. Patients were selected from diagnostic registries in medical genetic centers in Norway for cases of CMT4C. All patients were invited to complete a questionnaire and give medical consent to the use of clinical data from medical hospital records. A total of 35 patients from 31 families were found with CMT4C, which gives a minimum prevalence of 0.7/100,000 in Norway. Six new mutations were identified. Most patients had debut in the first decade with foot deformities, distal limb paresis, sensory ataxia and scoliosis. Proximal lower limb paresis and cranial nerve involvement was seen in about half of the patients. CMT4C is the most common recessive CMT in Norway. In addition to the classic distal limb affection, early debut, scoliosis, proximal paresis, cranial nerve affection and sensory ataxia are the most prominent features of CMT4C.

P233: Gender differences in intraepidermal nerve fiber density in healthy individuals and in patients with polyneuropathy

P234 – Figure 1. Nerve conduction studies in the sibling at 6 and 16 years. Abstract P234 – Figure 2. Nerve conduction studies in the father. clinical suspicion of small fiber neuropathy (SFN) or/and when a potential cause of SFN is present. Methods: Specimens were obtained through3 mmpunch skin biopsy 5-10 cmabove the lateral malleolus and sections were immunohistochemically stained for PGP 9.5. Analysis of IENFD was performed according to published guidelines. Data from patients (n=551, 313 females and 238 males) and healthy individuals (n=134, 77 females and 57 males) were available. Results: Mean IENFD in the controls was 12.4±4.5 and in the patient material 5.7±3.0 (p<0.001). Healthy females had significantly higher IENFD (13.6±4.7) than men (10.9±3.8, p=0.001), but this difference did not persist after adjustment for age (p=0.2). In the total patient group a significant gender difference in IENFD (in females 6.5±3.1; in males 4.8±2.5) existed also after adjustment for age (p<0.001). A similar difference between genders was also observed in the patients with abnormal IENFD (n=324), p=0.02, but not in patients with normal IENFD (n=227). Conclusions: In healthy individuals mean IENFD at the lower calf was lower in men than in women, but this difference did not persist after adjustment for age. However, in the total group of patients, as well as in those with abnormal IENFD depletion, males had significantly lower IENFD values than females.P234 – Figure 2. Nerve conduction studies in the father. clinical suspicion of small fiber neuropathy (SFN) or/and when a potential cause of SFN is present. Methods: Specimens were obtained through3 mmpunch skin biopsy 5-10 cmabove the lateral malleolus and sections were immunohistochemically stained for PGP 9.5. Analysis of IENFD was performed according to published guidelines. Data from patients (n=551, 313 females and 238 males) and healthy individuals (n=134, 77 females and 57 males) were available. Results: Mean IENFD in the controls was 12.4±4.5 and in the patient material 5.7±3.0 (p<0.001). Healthy females had significantly higher IENFD (13.6±4.7) than men (10.9±3.8, p=0.001), but this difference did not persist after adjustment for age (p=0.2). In the total patient group a significant gender difference in IENFD (in females 6.5±3.1; in males 4.8±2.5) existed also after adjustment for age (p<0.001). A similar difference between genders was also observed in the patients with abnormal IENFD (n=324), p=0.02, but not in patients with normal IENFD (n=227). Conclusions: In healthy individuals mean IENFD at the lower calf was lower in men than in women, but this difference did not persist after adjustment for age. However, in the total group of patients, as well as in those with abnormal IENFD depletion, males had significantly lower IENFD values than females. P234 Autosomal dominant intermediate Charcot-Marie-Tooth disease and nephropathy: clinical presentation and long-term follow-up M. Alcantara1, D. Portugal2, L.F. Oliveira3 1Sarah Rehabilitation Hospitals, Neurophysiology, Fortaleza, Brazil; 2Sarah Rehabilitation Hospitals, Neurology, Fortaleza, Brazil; 3Sarah Rehabilitation Hospitals, Pediatrics, Fortaleza, Brazil Question: Mutations in IFN2 and its interaction with formin related proteins might underlie the association of Charcot-Marie-Tooth disease (CMT) and neprhopathy. The usual phenotype is a neuropathy with intermediate conduction velocity range (25-45m/s) and nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS). It is currently unknown if the neurological deficits precede the renal disease and long term descriptions of the outcome are lacking.

P21-18 Evaluation of the small fiber involvement: Value of quantitative sensory testing

of LEPs between patients and controls (p = 0.37). The latency of P2 was prolonged in early symptomatic patients in comparison to asymptomatic PAF (p = 0.02), without significant differences between asymptomatic patients and controls. Conclusions: The amplitude of plantar SSR and LEP were sensitive measurements for detecting early small nerve fibers dysfunction. However, plantar SSR amplitude was the only abnormality detectable in asymptomatic carriers; its change should prompt us to a careful clinical and neurophysiological assessment. Longitudinal evaluation of asymptomatic carriers will allow us to determine its true predictive value.

286 DIFFERENCE BETWEEN HEAT PAIN AND WARM PERCEPTION THRESHOLDS IN PATIENTS WITH POLYNEUROPATHY AND HEALTHY INDIVIDUALS

Background and aims. Elderly individuals and patients with polyneuropathy often perceive heat pain instead of or almost at the same time as warm perception when quantitative sensory testing (QST) is performed. We therefore compared the difference between heat pain and warm perception thresholds (DiffHPWT) in order to explore whether this parameter is more strongly expressed in patients with peripheral neuropathy than in age and gender matched healthy individuals. Methods. Thirty six patients (23 women, 13 men, 52.8 + 12.2, range 33–75 years) with symptoms and signs of peripheral polyneuropathy matched according the age and gender with 36 healthy persons (53.0 + 12.3, range 34–74 years) were included. QST (using method of limits) was performed with SENSELab-THERMOTEST (Somedic, Sweden) recording warm, cold and heat pain perception thresholds on the distal calf and on the dorsal foot. DiffHP-WT in these locations was then calculated. Results. DiffHP-WT in the lower calf of the patients was 3.4 + 3.5 and 5.9 + 3.6 C in the controls (p = 0.007), while on the foot it was 3.6 + 2.9 versus 5.3 + 3.8 centigrades (p = 0.03). Only DiffHP-WT in the foot was significantly associated with age in patients (r = 0.63, p = 0.0001) as well as in controls (r = 0.45, p = 0.006). There were no differences between patients with and without neuropathic pain. Conclusions. QST with recording of temperature and pain perception thresholds is a useful and sensitive method in evaluation of patients with small fiber polyneuropathy. We propose difference between heat pain and warm perception thresholds (DiffHP-WT) as an additional parameter reflecting the functional condition of unmyelinated C-fibres.