Diagnostics and current care of myasthenia gravis.

Myasthenia gravis (MG) is the most common neuromuscular transmission disorder, causing weakness of skeletal muscles on exertion. The course of the disease is highly variable, symptoms and signs may change rapidly due to infection or pregnancy. MG is classified using serological, electrophysiological and pharmaceutical tools. A precise diagnosis allows for the choice of right treatment, predicts the course of disease and hence helps with the follow-up. In this review we present Finnish guidelines for diagnostics, treatment and follow-up of MG patients.

Decreased Aerobic Capacity in ANO5-Muscular Dystrophy.

BACKGROUND: Anoctaminopathies are muscle diseases caused by recessive mutations in the ANO5 gene. The effects of anoctaminopathy on oxidative capacity have not previously been studied in a controlled setting. OBJECTIVE: To characterize oxidative capacity in a clinically and genetically well-defined series of patients with anoctaminopathy. METHODS: We sequenced the ANO5 gene in 111 Finnish patients with suspected LGMD2. Patients with positive findings underwent close clinical examination, including electromyography, muscle MRI, and, in selected cases, muscle biopsy. Oxidative capacity was analyzed using spiroergometry and compared to age-matched healthy controls. RESULTS: We characterized 12 newly identified and 2 previously identified patients with ANO5 mutations from 11 families. Our material was genetically homogeneous with most patients homozygous for the Finnish founder variant c.2272C>T (p.Arg758Cys). In one family, we found a novel p.Met470Arg variant compound heterozygous with p.Arg758Cys. Lower limb muscle MRI revealed progressive fatty degeneration of specific posterior compartment muscles. Patients' spiroergometric profiles showed that anoctaminopathy significantly impaired oxidative capacity with increasing ventilation. CONCLUSIONS: Our findings support earlier reports that anoctaminopathy progresses slowly and demonstrate that the disease impairs the capacity for aerobic exercise.

Predicting Obstructive Sleep Apnea with Periodic Snoring Sound Recorded at Home.

STUDY OBJECTIVES: The cost-effectiveness of diagnosing obstructive sleep apnea (OSA) could be improved by using a preliminary screening method among subjects with no suspicion of other sleep disorders. We aimed to evaluate the diagnostic value of periodic snoring sound recorded at home. METHODS: We included 211 subjects, aged 18-83 (130 men), who were referred to our laboratory for suspicion of OSA, and had a technically successful overnight polygraphy, measured with the Nox T3 Sleep Monitor (Nox Medical, Iceland) with a built-in microphone. We analyzed the percentage of periodic snoring during the home sleep apnea study. RESULTS: Apnea-hypopnea index (AHI) ranged from 0.1 to 116 events/h and the percentage of periodic snoring from 1% to 97%. We found a strong positive correlation (r = 0.727, p < 0.001) between periodic snoring and AHI. The correlation was slightly stronger among female, younger, and obese subjects. The best threshold value of the periodic snoring for predicting an AHI > 15 events/h with as high sensitivity as possible was found to be 15%. There, sensitivity was 93.3%, specificity 35.1%, and negative predictive value 75.0%. CONCLUSIONS: According to our results, it is possible to set a periodic snoring threshold (15% or more) for the subject to advance to further sleep studies. Together with medical history and prior to more expensive studies, measuring periodic snoring at home is a simple and useful method for predicting the probability of OSA, in particular among women who are often unaware of their apnea-related snoring.

Progressive cranial nerve involvement and grading of facial paralysis in gelsolin amyloidosis.

INTRODUCTION: Hereditary gelsolin amyloidosis (GA) is a rare condition caused by the gelsolin gene mutation. The diagnostic triad includes corneal lattice dystrophy (type 2), progressive bilateral facial paralysis, and cutis laxa. Detailed information on facial paralysis in GA and the extent of cranial nerve injury is lacking. METHODS: 29 GA patients undergoing facial corrective surgery were interviewed, examined, and studied electroneurophysiologically. RESULTS: All showed dysfunction of facial (VII) and trigeminal (V) nerves, two-thirds of oculomotor (III) and hypoglossal (XII) nerves, and half of vestibulocochlear (acoustic) (VIII) nerve. Clinical involvement of frontal, zygomatic, and buccal facial nerve branches was seen in 97%, 83%, and 52% of patients, respectively. Electromyography showed marked motor unit potential loss in facial musculature. CONCLUSIONS: Cranial nerve involvement in GA is more widespread than previously described, and correlates with age, severity of facial paralysis, and electromyographic findings. We describe a grading method for bilateral facial paralysis in GA, which is essential for evaluation of disease progression and the need for treatment.

Intravenous lipid emulsion given to volunteers does not affect symptoms of lidocaine brain toxicity.

Intravenous lipid emulsion has been suggested as treatment for local anaesthetic toxicity, but the exact mechanism of action is still uncertain. Controlled studies on the effect of lipid emulsion on toxic doses of local anaesthetics have not been performed in man. In randomized, subject-blinded and two-phase cross-over fashion, eight healthy volunteers were given a 1.5 ml/kg bolus of 20% Intralipid(®) (200 mg/ml) or Ringer's acetate solution intravenously, followed by a rapid injection of lidocaine 1.0 mg/kg. Then, the same solution as in the bolus was infused at a rate of 0.25 ml/kg/min. for 30 min. Electroencephalography (EEG) was recorded, and 5 min. after lidocaine injection, the volunteers were asked to report subjective symptoms. Total and un-entrapped lidocaine plasma concentrations were measured from venous blood samples. EEG band power changes (delta, alpha and beta) after the lidocaine bolus were similar during lipid and during Ringer infusion. There were no differences between infusions in the subjective symptoms of central nervous system toxicity. Lidocaine was only minimally entrapped in the plasma by lipid emulsion, but the mean un-entrapped lidocaine area under concentration-time curve from 0 to 30 min. was clearly smaller during lipid than Ringer infusion (16.4 versus 21.3 mg × min/l, p = 0.044). Intravenous lipid emulsion did not influence subjective toxicity symptoms nor affect the EEG changes caused by lidocaine.

Frontal electroencephalogram variables are associated with the outcome and stage of hepatic encephalopathy in acute liver failure.

Acute liver failure (ALF) and hepatic encephalopathy (HE) can lead to an elevated intracranial pressure (ICP) and death within days. The impaired liver function increases the risks of invasive ICP monitoring, whereas noninvasive methods remain inadequate. The purpose of our study was to explore reliable noninvasive methods of neuromonitoring for patients with ALF in the intensive care unit (ICU) setting; more specifically, we wanted to track changes in HE and predict the outcomes of ALF patients treated with albumin dialysis. The study included 20 patients with severe ALF at admission who had been referred to the ICU of the liver transplantation (LT) center for albumin dialysis treatment and evaluation for transplantation. Data were collected from all study patients in the form of continuous frontal electroencephalography (EEG) recordings and transcranial Doppler (TCD) measurements of cerebral blood flow. Among the studied EEG variables, the 50% spectral edge frequency decreased and the delta power increased as the HE stage increased. Both variables were predictive of the stage of HE [prediction probability (PK) of 50% spectral edge frequency = 0.23, standard error (SE) = 0.03; PK of delta power = 0.76, SE = 0.03]. The total wavelet subband entropy, a novel variable that we used for tracking abnormal EEG activity, predicted the outcome of ALF patients treated with albumin dialysis (PK = 0.88, SE = 0.09). With a threshold value of 1.6, the TCD pulsatility index had an odds ratio of 1.1 (95% confidence interval = 0.1-9.3) for a poor outcome (LT or death). In conclusion, EEG variables are useful for the monitoring of HE and can be used to predict outcomes of ALF. TCD measurements do not predict patient outcomes.

Screening of snoring with an MP3 recorder.

PURPOSE: Snoring patients seeking medical assistance represent a wide range of clinical and sleep study findings from nonsleepy nonapneic snoring to severe obstructive sleep apnea syndrome. The prevalence of snoring is high and it significantly impacts quality of life. Its objective diagnosis usually requires a sleep study. We developed a system to analyze snoring sounds with a Moving Picture Experts Group Layer-3 Audio (MP3) recorder device and present its value in the screening of snoring. METHODS: We recorded snoring sounds during in-lab polysomnography (PSG) in 200 consecutive patients referred for a suspicion of obstructive sleep apnea. Snoring was recorded during the PSG with two microphones: one attached to the throat and the other to the ceiling; an MP3 device was attached to the patient's collar. Snoring was confirmed when the MP3 acoustic signal exceeded twice the median value of the acoustic signal for the entire recording. Results of the MP3 snoring recording were compared to the snoring recordings from the PSG. RESULTS: MP3 recording proved technically successful for 87% of the patients. The Pearson correlation between PSG snoring and MP3 snoring was highly significant at 0.77 (p < 0.001). The MP3 recording device underestimated the snoring time by a mean ± SD of 32 ± 55 min. CONCLUSIONS: The recording of snoring with an MP3 device provides reliable information about the patient's snoring.

Cyclic alternating pattern is associated with cerebral hemodynamic variation: a near-infrared spectroscopy study of sleep in healthy humans.

The cyclic alternating pattern (CAP), that is, cyclic variation of brain activity within non-REM sleep stages, is related to sleep instability and preservation, as well as consolidation of learning. Unlike the well-known electrical activity of CAP, its cerebral hemodynamic counterpart has not been assessed in healthy subjects so far. We recorded scalp and cortical hemodynamics with near-infrared spectroscopy on the forehead and systemic hemodynamics (heart rate and amplitude of the photoplethysmograph) with a finger pulse oximeter during 23 nights in 11 subjects. Electrical CAP activity was recorded with a polysomnogram. CAP was related to changes in scalp, cortical, and systemic hemodynamic signals that resembled the ones seen in arousal. Due to their repetitive nature, CAP sequences manifested as low- and very-low-frequency oscillations in the hemodynamic signals. The subtype A3+B showed the strongest hemodynamic changes. A transient hypoxia occurred during CAP cycles, suggesting that an increased CAP rate, especially with the subtype A3+B, which may result from diseases or fragmented sleep, might have an adverse effect on the cerebral vasculature.

Spontaneous hemodynamic oscillations during human sleep and sleep stage transitions characterized with near-infrared spectroscopy.

Understanding the interaction between the nervous system and cerebral vasculature is fundamental to forming a complete picture of the neurophysiology of sleep and its role in maintaining physiological homeostasis. However, the intrinsic hemodynamics of slow-wave sleep (SWS) are still poorly known. We carried out 30 all-night sleep measurements with combined near-infrared spectroscopy (NIRS) and polysomnography to investigate spontaneous hemodynamic behavior in SWS compared to light (LS) and rapid-eye-movement sleep (REM). In particular, we concentrated on slow oscillations (3-150 mHz) in oxy- and deoxyhemoglobin concentrations, heart rate, arterial oxygen saturation, and the pulsation amplitude of the photoplethysmographic signal. We also analyzed the behavior of these variables during sleep stage transitions. The results indicate that slow spontaneous cortical and systemic hemodynamic activity is reduced in SWS compared to LS, REM, and wakefulness. This behavior may be explained by neuronal synchronization observed in electrophysiological studies of SWS and a reduction in autonomic nervous system activity. Also, sleep stage transitions are asymmetric, so that the SWS-to-LS and LS-to-REM transitions, which are associated with an increase in the complexity of cortical electrophysiological activity, are characterized by more dramatic hemodynamic changes than the opposite transitions. Thus, it appears that while the onset of SWS and termination of REM occur only as gradual processes over time, the termination of SWS and onset of REM may be triggered more abruptly by a particular physiological event or condition. The results suggest that scalp hemodynamic changes should be considered alongside cortical hemodynamic changes in NIRS sleep studies to assess the interaction between the autonomic and central nervous systems.

Recovery of brachial plexus lesions resulting from heavy backpack use: a follow-up case series.

BACKGROUND: Brachial plexus lesions as a consequence of carrying a heavy backpack have been reported, but the typical clinical course and long-term consequences are not clear. Here we evaluated the clinical course and pattern of recovery of backpack palsy (BPP) in a large series of patients. METHODS: Thirty-eight consecutive patients with idiopathic BPP were identified from our population of 193,450 Finnish conscripts by means of computerised register. A physiotherapist provided instructions for proper hand use and rehabilitative exercises at disease onset. The patients were followed up for 2 to 8 years from the diagnosis. We also searched for genetic markers of hereditary neuropathy with pressure palsies. Mann-Whitney U-test was used to analyze continuous data. The Fischer's exact test was used to assess two-way tables. RESULTS: Eighty percent of the patients recovered totally within 9 months after the onset of weakness. Prolonged symptoms occurred in 15% of the patients, but daily activities were not affected. The weight of the carried load at the symptom onset significantly affected the severity of the muscle strength loss in the physiotherapeutic testing at the follow-up. The initial electromyography did not predict recovery. Genetic testing did not reveal de novo hereditary neuropathy with pressure palsies. CONCLUSIONS: The prognosis of BPP is favorable in the vast majority of cases. Electromyography is useful for diagnosis. To prevent brachial plexus lesions, backpack loads greater than 40 kg should be avoided.

Progressive Stroke-Like Symptoms in a Patient with Sporadic Creutzfeldt-Jakob Disease.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in which accumulation of a pathogenic isoform of prion protein (PrP(Sc)) induces neuronal damage with distinct pathologic features. The prognosis of sCJD is devastating: rapid clinical decline is followed by death generally within months after onset of symptoms. The classic clinical manifestations of sCJD are rapidly progressing dementia, myoclonus, and ataxia. However, the spectrum of clinical features can vary considerably. We describe a definite, neuropathologically verified sCJD in a 67-year-old woman who initially presented with progressive stroke-like symptoms: left-sided hemiparesis and ataxia within a few days. The initial brain magnetic resonance imaging (MRI) showed bilateral cortical hyperintensity on diffusion-weighted sequences (DWI) resembling multiple ischemic lesions. Despite anticoagulation with low-molecular-weight heparin, the patient deteriorated rapidly, became dysphagic and bedridden with myoclonic jerks on her left side extremities correlating with intermittent high-amplitude epileptiform discharges on electroencephalography (EEG). Basal ganglia hyperintense signal changes in addition to cortical ribboning were seen in DWI images of a follow-up MRI. Repeated EEG recordings showed an evolution to periodic sharp wave complexes. Protein 14-3-3 was positive in her cerebrospinal fluid specimen, in addition to an abnormally high total tau level. In the terminal stage the patient was in an akinetic, mutistic state with deteriorating consciousness. She died 19 days after admission to the hospital. Neuropathologic investigation corroborated the clinical diagnosis of sCJD with spongiform degeneration and immunohistochemical demonstration of the deposition of pathologic PrP(Sc).

[EEG examination in emergency medicine and analysis of unconciousness]. / Elektroenkefalografia päivystyslääketieteessä ja tajuttomuuden selvittelyssä.

For a long time, the EEG examination has been used as a laboratory examination especially in the diagnostics of epilepsy, but both technical difficulties and problems in interpretation have limited its use in emergency medicine outside special neurological intensive care units. Development of monitoring technology and easier data transfer is making EEG monitoring possible also in the emergency area. The greatest need focuses on the diagnostics and treatment of status epilepticus underlying an unclear unconsciousness. In other indications the usually required information can be obtained by daytime measurements.

Hypothermia-treated cardiac arrest patients with good neurological outcome differ early in quantitative variables of EEG suppression and epileptiform activity.

OBJECTIVE: To evaluate electroencephalogram-derived quantitative variables after out-of-hospital cardiac arrest. DESIGN: Prospective study. SETTING: University hospital intensive care unit. PATIENTS: Thirty comatose adult patients resuscitated from a witnessed out-of-hospital ventricular fibrillation cardiac arrest and treated with induced hypothermia (33 degrees C) for 24 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Electroencephalography was registered from the arrival at the intensive care unit until the patient was extubated or transferred to the ward, or 5 days had elapsed from cardiac arrest. Burst-suppression ratio, response entropy, state entropy, and wavelet subband entropy were derived. Serum neuron-specific enolase and protein 100B were measured. The Pulsatility Index of Transcranial Doppler Ultrasonography was used to estimate cerebral blood flow velocity. The Glasgow-Pittsburgh Cerebral Performance Categories was used to assess the neurologic outcome during 6 mos after cardiac arrest. Twenty patients had Cerebral Performance Categories of 1 to 2, one patient had a Cerebral Performance Categories of 3, and nine patients had died (Cerebral Performance Categories of 5). Burst-suppression ratio, response entropy, and state entropy already differed between good (Cerebral Performance Categories 1-2) and poor (Cerebral Performance Categories 3-5) outcome groups (p = .011, p = .011, p = .008) during the first 24 hrs after cardiac arrest. Wavelet subband entropy was higher in the good outcome group between 24 and 48 hrs after cardiac arrest (p = .050). All patients with status epilepticus died, and their wavelet subband entropy values were lower (p = .022). Protein 100B was lower in the good outcome group on arrival at ICU (p = .010). After hypothermia treatment, neuron-specific enolase and protein 100B values were lower (p = .002 for both) in the good outcome group. The Pulsatility Index was also lower in the good outcome group (p = .004). CONCLUSIONS: Quantitative electroencephalographic variables may be used to differentiate patients with good neurologic outcomes from those with poor outcomes after out-of-hospital cardiac arrest. The predictive values need to be determined in a larger, separate group of patients.

Severe ataxia with neuropathy in hereditary gelsolin amyloidosis.

Hereditary gelsolin amyloidosis (AGel amyloidosis) is a systemic disorder caused by a G654A or G654T gelsolin mutation, reported from Europe, North America, and Japan. Principal clinical signs are corneal lattice dystrophy, cutis laxa and cranial neuropathy, often deleterious at advanced age. Peripheral neuropathy, if present, is usually mild. We report a 78- year old male Finnish patient who presented with ataxia and mainly sensory peripheral polyneuropathy (PNP) signs, causing severe disability and ambulation loss. Electrophysiological studies showed severe generalized chronic mainly axonal sensorimotor PNP with facial paralysis. In magnetic resonance imaging proximal lower limb and axial muscle atrophy with fatty degeneration as well as moderate spinal cord atrophy were seen. A G654A gelsolin mutation was demonstrated but no other possible causes of his disability were found. At age 79 he became bedridden and died of pulmonary embolism. Neuropathological examination revealed marked gelsolin amyloid deposition at vascular and connective tissue sites along the entire length of the peripheral nerves extending to the spinal nerve roots, associated with severe degeneration of nerve fibers and posterior columns. Our report shows that advanced AGel amyloidosis due to degeneration of central and distal sensory nerve projections results in deleterious ataxia with fatal outcome. Severe posterior column atrophy may reflect radicular AGel deposition, although even altered gelsolin - actin interactions in neural cells possibly contribute to neurodegeneration with successive ataxia in carriers of a G654A gelsolin mutation.

[Update on current care guidelines. The treatment of status epilepticus]. / Pitkittynyt epileptinen kohtaus.

Status epilepticus is a medical emergency. Most epileptic seizures last for 1-4 minutes and seizures lasting over five minutes, should be treated as status epilepticus. EEG is essential for diagnostics and the monitoring of treatment effect. The treatment for status epilepticus, irrespective of aetiology, can be divided into first-aid medications, such as buccal midazolam or rectal diazepam, first-line medications such as intravenous diazepam or lorazepam, and second-line medications such as fosphenytoin and valproate for adults and phenobarbital for children. Third-line treatment is suppressive general anaesthesia, monitored by continuous EEG. Antiepileptic medication of patients with epilepsy should be carefully re-evaluated after episode of status epilepticus.

Prediction of poor outcome using detector of epileptiform EEG in ICU patients resuscitated after cardiac arrest.

Assessing the brain status of patients admitted to intensive care unit (ICU) after out-of-hospital cardiac arrest is challenging. We had earlier found wavelet subband entropy (WSE) to be a useful tool for quantifying the epileptiform content of EEG during anesthesia. In this paper, WSE was applied for EEG of ICU patients to study its prognostic value. During their stay in ICU, EEG was recorded from 20 patients resuscitated after out-of-hospital cardiac arrest. For the analysis, the patients were divided into subgroups of poor outcome (persistent vegetative state, N=4) and good outcome (regain of consciousness, N=16). WSE for each 5-sec segment of EEG was calculated and also the average of WSE for each hour. Also, similar results were calculated for EEG powers in the bands 16-32 Hz and 1-60 Hz to be used as references. The statistical analysis was made by comparing the medians of the distributions of average WSE of each hour between poor and good outcome groups. The median of WSE of poor outcome group was significantly lower than that of good outcome group. The reference indicators did not show significant differences between the groups. The results suggest that WSE can be a valuable prognostic indicator for detecting the patients with poor outcome.

Dysphonia and dysphagia after anterior cervical decompression.

OBJECT: In this paper, the authors investigate the effects of anterior cervical decompression (ACD) on swallowing and vocal function. METHODS: The study comprised 114 patients who underwent ACD. The early group (50 patients) was examined immediately pre- and postoperatively, and the late group (64 patients) was examined at only 3 to 9 months postoperatively. Fifty age- and sex-matched patients from the Department of Otorhinolaryngology-Head and Neck Surgery who had not been intubated in the previous 5 years were used as a control group. All patients in the early and control groups were examined by a laryngologist; patients in the late group were examined by a laryngologist and a neurosurgeon. Videolaryngostroboscopy was performed in all members of the patient and control groups, and the function of the ninth through 12th cranial nerves were clinically evaluated. Data were collected concerning swallowing, voice quality, surgery results, and health-related quality of life. Patients with persistent dysphonia were referred for phoniatric evaluation and laryngeal electromyography (EMG). Those with persistent dysphagia underwent transoral endoscopic evaluation of swallowing function and videofluorography. RESULTS: Sixty percent of patients in the early group reported dysphonia and 69% reported dysphagia at the immediate postoperative visit. Unilateral vocal fold paresis occurred in 12%. The prevalence of both dysphonia and dysphagia decreased in both groups 3 to 9 months postoperatively. All six patients with vocal fold paresis in the early group recovered, and in the late group there were two cases of vocal fold paresis. The results of laryngeal EMG were abnormal in 14 of 16 patients with persistent dysphonia. Neither intraoperative factors nor age or sex had any effect on the occurrence of dysphonia, dysphagia, or vocal fold paresis. Most patients were satisfied with the surgical outcome. CONCLUSIONS: Dysphonia, dysphagia, and vocal fold paresis are common but usually transient complications of ACD. Recurrent laryngeal nerve damage detected by EMG is not rare. Pre-and postoperative laryngeal examination of ACD patients should be considered.

Smoking and improvement after nasal surgery in snoring men.

BACKGROUND: The aim of this study was to compare subgroups of smokers and nonsmokers undergoing nasal surgery and to evaluate improvement of nasal stuffiness, snoring, and symptoms related to sleep-disordered breathing after nasal surgery. METHODS: A cross-sectional prospective study was performed. The study population included 40 consecutive snoring men scheduled for surgical treatment of nasal obstruction. The patients completed nasal and sleep questionnaires, an Epworth sleepiness scale, and a visual analog scale of snoring intensity. They underwent polysomnography, anterior rhinomanometry, acoustic rhinometry, and cephalometric analysis. RESULTS: The smokers were younger, they snored longer and louder, and they had higher nasal resistance with decongestion and longer soft palates than the nonsmokers. Nasal stuffiness improved well after surgery, but a decrease of nasal resistance was not related to improvement of subjective snoring. CONCLUSION: Smoking was associated with increased snoring, nasal obstruction, and pharyngeal soft tissue volume. Expectations of patients may influence subjective assessment of snoring after nasal surgery.

Severe ataxia with neuropathy in hereditary gelsolin amyloidosis: a case report.

Hereditary gelsolin amyloidosis (AGel amyloidosis) is a systemic disorder caused by a G654A or G654T gelsolin mutation, reported from Europe, North America, and Japan. Principal clinical signs are corneal lattice dystrophy, cutis laxa and cranial neuropathy, often deleterious at advanced age. Peripheral neuropathy, if present, is usually mild. We report a 78-year-old male Finnish patient who presented with ataxia and mainly sensory peripheral polyneuropathy (PNP) signs, causing severe disability and ambulation loss. Electrophysiological studies showed severe generalized chronic mainly axonal sensorimotor PNP with facial paralysis. In magnetic resonance imaging proximal lower limb and axial muscle atrophy with fatty degeneration as well as moderate spinal cord atrophy were seen. A G654A gelsolin mutation was demonstrated but no other possible causes of his disability were found. At age 79 years he became bedridden and died of pulmonary embolism. Neuropathological examination revealed marked gelsolin amyloid deposition at vascular and connective tissue sites along the entire length of the peripheral nerves extending to the spinal nerve roots, associated with severe degeneration of nerve fibers and posterior columns. Our report shows that advanced AGel amyloidosis due to degeneration of central and distal sensory nerve projections results in deleterious ataxia with fatal outcome. Severe posterior column atrophy may reflect radicular AGel deposition, although even altered gelsolin-actin interactions in neural cells possibly contribute to neurodegeneration with successive ataxia in carriers of a G654A gelsolin mutation.