Continuous Motor Unit Activity Research Articles

A rare presentation of stiff-person syndrome with a nonspecific focal myositis: A case report

Introduction. The stiff-person syndrome (SPS) is a rare disease whose incidence is estimated at approximately 1 in a million individuals in the general population. Diagnosis relies on a combination of clinical, immunological, and electromyographic items. We present the case of a patient diagnosed with the idiopathic SPS, initially misdiagnosed as focal paravertebral myositis. Case presentation. A 36-year-old patient was referred to us for the investigation of subacute dorsal myalgias. The patient reported a severe torticollis seven months ago, which resolved spontaneously after one month, and some episodes of back stiffness. On examination, the patient was afebrile, had hyperlordosis with a paravertebral contracture and tenderness. Neurological and cognitive examinations were normal. C-reactive protein was at 137 mg/l. The rest of laboratory investigations, including creatine phosphokinase (CPK), were within normal range. Spinal MRI revealed T2 hyperintensity in the semispinalis muscle, erector spinae muscle, trapezius muscle, as well as the intervertebral muscles. Therefore, focal paravertebral myositis was suspected. The electromyogram (EMG) revealed the presence of a continuous motor unit activity in agonist and antagonist muscles, suggestive of stiff-person syndrome. Antinuclear antibodies, anti-glutamic acid decarboxylase 65 and onconeuronal antibodies were negative. Analysis of the cerebrospinal fluid, including anti-glutamic acid decarboxylase 65 test, was normal. We noticed that the paravertebral contracture became less noticeable when the patient was commenced on diazepam. Diagnosis of SPS was established according to Dalakas criteria. Investigations for an underlying neoplasm, were normal. Associated autoimmune disorders have been ruled out. The MRI description was rather explained by the continuous contraction of the affected muscles. Treatment included diazepam, baclofen, intravenous immunoglobulin and corticosteroids. The patient showed important signs of improvement. Conclusion. SPS is a rare condition whose diagnosis can be delayed. Recognizing and managing SPS as early as possible is crucial. It is based on clinical reasoning, imaging, biological features and EMG.

THU356 Muscle Pain In A Diabetic: Think Outside The Box

Abstract Disclosure: R. Ellangovan: None. M. Rizk: None. V. Singh MD: None. C. Sherpa: None. Introduction: Stiff person syndrome (SPS) is a rare immunological disorder associated with GAD antibody-spectrum disorders and characterized by rigidity and painful muscle spasms. SPS has a prevalence of 1-2 cases per million and affects females more than men. We present a case of SPS who was admitted for progressive muscle pain and rigidity causing impaired ambulation. Case Presentation: A 60-year-old female with a two-year history of type 2 diabetes, Graves' disease was diagnosed with acral lentiginous melanoma of the left foot. One month after Nivolumab immunotherapy, she converted to type 1 diabetes with low C-peptide and positive GAD antibody. She was admitted with severe muscle pain and spasms in her lower extremities and trunk, debilitating enough to make her bedbound. Her muscle strength and sensory function were intact. MRI of thigh was concerning for myositis versus diabetic myonecrosis. She was initiated on NSAIDs with no improvement. Core muscle biopsy revealed necrosis and granulation tissue with no evidence of malignancy. Extensive work up including myositis panel and myasthenia gravis panel were negative. The presence of GAD antibodies and no improvement to NSAIDs, prompted suspicion for SPS. The patient declined lumbar puncture (LP) for further evaluation. Diazepam showed mild improvement. Due to persistent severe symptoms, she was treated with IVIG for 5 days that resulted in marked improvement. Discussion: There is no gold standard test for definitive diagnosis of SPS. Classic features of SPS include muscle spasms, pain, and rigidity typically involving the trunk and lower extremities. There are GAD antibodies in serum and CSF and glycine receptor or amphiphysin antibodies. EMG study will show continuous motor unit activity in affected muscles. A robust response to muscle relaxants like GABA agonists and exclusion of alternative neurological disorder favors SPS. LP or EMG was not performed on this patient, yet she met other criteria including the presence of other GAD disorders like type 1 diabetes. Current recommended therapy for symptomatic relief includes GABA agonists or baclofen. If no improvement is noted, IVIG can be considered. Plasmapheresis and rituximab have been used with variable efficacy. Prognosis is variable and many patients experience disability despite combining multiple therapies. Hence it is crucial to have a high index of suspicion in GAD spectrum disorders for early recognition and prompt treatment. Presentation: Thursday, June 15, 2023

Teaching Video NeuroImage: Hung-Up Reflex in Stiff Limb Syndrome.

A 45-year-old woman developed an intermittent gait disorder and agoraphobia that was initially diagnosed as a functional movement disorder (FMD). Examination revealed fluctuating left leg stiffness with a hung-up reflex (Video 1). Neuroimaging and laboratory testing were normal (including thyroid function). EMG showed continuous motor unit activity in the left leg muscles. Elevated serum (>2,000 U/mL) and CSF (21.09 U/mL) GAD65 antibodies were found consistent with stiff limb syndrome, a rare variant of stiff-person syndrome (SPS). Symptoms responded to diazepam. The hung-up reflex has been classically described in hypothyroidism and Huntington disease,1 and this case suggests that it may also be a feature of SPS.2 This clinical finding should be kept in mind when assessing patients with FMD.

P-NE014. Electromyography in the diagnosis of stiff-person syndrome

Introduction . Stiff-person syndrome (SPS) is a rare autoimmune or paraneoplastic disorder with a wide clinical spectrum but core features of trunk and limb stiffness and muscle spasms. It is commonly associated with glutamic acid decarboxylase (GAD 65) antibody and responds to treatment with benzodiazepines and immunotherapy. We present the details of a patient with SPS and highlight the diagnostic utility of electromyography (EMG). Results . A 58-years-old man developed progressive asymmetric stiffness of both lower limbs and walking difficulty of ten months duration. Superimposed on that, he had painful spasms of lower limb which were triggered by sound or touch. On examination, he was found to have asymmetric hypertonia in both lower limbs and gait difficulty requiring the assistance of two- persons to walk. Serum GAD-65 antibody was strongly positive. He underwent electrophysiological evaluation. Nerve conduction studies were normal. Lower limb surface EMG with recording from quadriceps, hamstrings, tibialis anterior, and lateral head of gastrocnemius on the right side and quadriceps and hamstrings on the left side was performed. It showed continuous motor unit activity in agonist and antagonist muscle groups. After the administration of diazepam, the motor unit activity reduced significantly while stimulation with a loud sound led to an increased in activity. Based on these findings, he was diagnosed with SPS and treated with immunotherapy and symptomatic medications. He had significant improvement and was able to walk independently at four months of follow up. Conclusion . SPS is a rare but treatable neurological illness that can be confused with many other disorders like parkinsonism, dystonia, musculoskeletal, psychogenic, etc. EMG can provide a useful clue to the diagnosis by demonstrating characteristic continuous motor unit activity in agonist and antagonist muscles which triggered by specific stimuli and improved with diazepam.

Case Report: Dexmedetomidine for Intractable Clusters of Myoclonic Jerks and Paroxysmal Sympathetic Hyperactivity in Progressive Encephalomyelitis With Rigidity and Myoclonus

Introduction: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a severe form of stiff-person spectrum disorder characterized by painful spasms, myoclonic jerks, hyperekplexia, brainstem dysfunction, and dysautonomia, which is sometimes resistant to γ-amino-butyric acid (GABA)-ergic agents. The response to immunotherapy varies depending on identified autoantibodies. We report a dramatic response to dexmedetomidine in a patient with glycine receptor (GlyR) antibody-positive PERM who developed intractable clusters of myoclonic jerks and paroxysmal sympathetic hyperactivity (PSH) that was highly refractory to conventional symptomatic treatment with GABAergic drugs and immunotherapy.Case Presentation: A 62-year-old Japanese man was transferred to our center for intermittent painful spasms that progressed in severity over the preceding 7 weeks. On admission, he had gaze-evoked nystagmus, and paroxysmal painful spasms/myoclonic jerks triggered by sound or touch. The myoclonic jerks rapidly worsened, along with the development of hyperekplexia, opisthotonus, and PSH, leading to prolonged apnea requiring mechanical ventilation. Brain and spinal cord magnetic resonance imaging was unremarkable. Cerebrospinal fluid (CSF) examination revealed mild pleocytosis and oligoclonal bands. Surface electromyography confirmed simultaneous agonist-antagonist continuous motor unit activity. Based on the clinico-electrophysiological features, PERM was suspected. He was initially treated with intravenous steroids, immunoglobulin, benzodiazepines, and propofol, but the symptoms persisted. On day 9, he received a continuous infusion of dexmedetomidine, which resulted in dramatic reduction in the frequency of clusters of myoclonic jerks and PSH. The effect of dexmedetomidine was confirmed by surface electromyography. The addition of plasma exchange resulted in further clinical improvement. GlyR antibodies were identified in the CSF but not the serum, leading to the diagnosis of GlyR antibody-positive PERM.Conclusions: PERM is an immune-mediated disorder, but dexmedetomidine, a highly selective α2-adrenergic agonist, may alleviate paroxysmal symptoms by decreasing noradrenergic neuronal activity, resulting in attenuation of antibody-mediated disinhibited increased motor and sympathetic activity. Dexmedetomidine may be useful as an adjunctive symptomatic therapy in PERM and related disorders.

An Appraisal of Electrodiagnostic Studies in Stiff Person Syndrome.

A literature review was performed on the use of electrodiagnostic (EDX) tests including nerve conduction study, electromyography, exteroceptive reflex, blink reflex, and late response in the evaluation of patients with stiff person syndrome (SPS). A web survey was conducted to report the extent of EDX testing usage in the evaluation of SPS among laboratories accredited by the American Academy of Neuromuscular and Electrodiagnostic Medicine. Coactivation of selected agonist and antagonist muscles was performed in 5 healthy subjects to determine its specificity for SPS. Observation of continuous motor unit activity on electromyography and elicitation of exteroceptive reflexes by electric stimulation are informative in assisting a diagnosis of SPS, but further studies focusing on their sensitivities in diagnosing SPS and specificities in differentiating SPS from other movement disorders are needed. The value of EDX testing in SPS lies in ruling out other neuromuscular disorders.

Facial muscle activity contaminates EEG signal at rest: evidence from frontalis and temporalis motor units

Objective. In order to reach electroencephalography (EEG) electrodes on the scalp, synchronized activity of neurons needs to pass thorough several tissue layers, including the skull and muscles covering the scalp. The contamination of EEG signal by temporalis and frontalis muscles has been well documented for voluntary muscle contraction even at low contraction levels. The extent of myogenic contamination during postural and/or rest activity of the temporalis and frontalis remains an impediment for EEG research. Approach. In this study, we first aimed to observe involuntary, continuous motor unit activity of the frontalis muscle at rest and evaluate motor unit level frontalis interference on the EEG electrodes. Second, we compared motor unit interference from the frontalis before and after artefact pruning via an independent component analysis (ICA) algorithm. Main results. We demonstrated that motor unit activity of the frontalis muscle produces interference potentials on the frontal electrodes at rest and the interference was significantly reduced after ICA on the frontal electrodes, but not completely eliminated. Likewise, the temporalis interference at rest was significantly smaller after ICA on the fronto-temporal electrodes, but not completely removed. Significance. We documented the existence of resting involuntary activity of the temporalis and frontalis muscles underneath EEG electrodes and the removal of the EEG signal from their contiguous interference is not possible even after the use of ICA technology. We recommend that EEG researchers readdress the definition of ‘rest’ for EEG recordings and the ICA experts should extend their electromyography removal strategies to motor unit level interference.

O-35 The Stiff Person Syndrome. Neurophysiological findings

Background Stiff Person Syndrome (SPS) an encephalomyelitis, is an immune-mediated disorder characterized by rigidity of the axial and proximal limb muscles with painful spasThis rare disease responds to immunotherapies and is frequently associated with other autoimmune diseases. More than 80% of SPS patients have autoantibodies to GAD65 and up to 15% have antibodies to glycinereceptor. Neurophysiological studies can help in the diagnosis by demonstrating the presence of continuous motor unit activity at rest, that the patient cannot voluntarily suppress. Material and methods We present a male patient 28 y/o with a history of weight loss, abdominal pain, ortostathic hypotension, ptosis and babinski sign, whith stiffness and painful spasms in both cuadriceps, tibialis anterior, gastronemius, rectus abdominis, thoracic and lumbar paraspinal muscles. Results EMG showed continuous, involuntary activity of normal motor unit potentials. Painful spasms of involuntary muscle activity, were also detected. No other abnormal spontaneus activity such as fibrilations, positive waves, miokimias, high frequency nor myotonic or neuromyotonic discharges were recorded. The SSR was absent en both hands. The Silent period was normal. ENG and SFEMG were normal. Antibodies to glycinereceptors were positive. After treatment with IvIg and plasma exchange the patient had moderate improvement and at present he is on baclofen, diazepam, methylprednisone and levetirazetam, with persistence of fluctuating stiffness and spas. Conclusions The neurophysiological studies play an important role in the differential diagnosis of the diseases associated with excess motor unit activity, leading in this patient to the diagnosis of encephalomyelitis with rigidity, variant of SPS.

P.026 Acute lower limb spasticity: Stiff person syndrome responsive to immunomodulatory therapy in an adolescent female

Background: Stiff person syndrome (SPS) is a rare disorder presenting with progressive stiffness and spasms of the musculature of the trunk and limbs. SPS is reported very rarely in children and adolescents, with 5 cases over 25 years in a recent 99 patient cohort. Methods: Case Study Results: Herein we report a 15 year old female, presenting with acute onset of rapidly progressive spasticity of the lower extremities. Initial exam was remarkable for markedly limited left knee range of motion, in addition to asymmetrical knee spastic catch and hyper-reflexia. EMG revealed almost continuous motor unit activity which dissipated with voluntary muscle contraction. Diagnosis was confirmed by high titres of glutamate decarboxylase (GAD65) antibodies >25,000 units/ml. The patient was initially treated with IVIG, baclofen, and diazepam followed by IV methylprednisolone, with mild subjective improvements. One day following the first rituximab treatment, she achieved spontaneous knee flexion and regained the ability to ambulate independently. There is a residual spastic catch at the knees. Conclusions: This case highlights that SPS, albeit extremely rare, should be considered in the differential diagnosis of acquired spasticity in children. Also noteworthy is the relatively rapid resumption of function with aggressive immunomodulatory treatments in this historically devastating disorder.

A case of stiff dog syndrome associated with anti-glutamic acid decarboxylase antibodies

BackgroundThe stiff person syndrome (SPS) is a rare and debilitating autoimmune disorder with an unknown pathogenesis and variable clinical presentation that can present a diagnostic challenge. Although entities that clinically mimic stiff-person spectrum disorders (SPSD) have manifested in horses, they have not been reported in dogs.Case presentationWe describe a 2-year-old beagle dog presented for progressive attacks of muscular rigidity and lordosis with superimposed spasms of the appendicular muscles triggered by tactile stimulation which resulted in marked gait impairment. Resting electromyography revealed continuous motor unit activity in the axial musculature. Compared to age-matched healthy beagle dogs, this patient had elevated glutamic acid decarboxylase antibody concentrations in serum and cerebrospinal fluid.ConclusionThis dog presented with phenotypic, electrodiagnostic, and immunologic criterion consistent with an SPSD, including elevated anti-GAD antibody titers, which we have termed the “stiff dog syndrome (SDS)”. Durable clinical improvement was achieved with symptomatic and immunosuppressive treatments including baclofen, gabapentin, prednisone, and intravenous immunoglobulin.

Thymic Abnormalities and Stiff Person Syndrome

SESSION TITLE: Global Case Report Poster - Cardiothoracic Surgery SESSION TYPE: Global Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Stiff Person Syndrome (SPS) is a rare autoimmune neurological disorder characterized by painful muscle spasms and rigidity. It may be seen in association with other autoimmune diseases, and 60% of patients have anti-glutaminic acid decarboxylase (GAD) antibodies. There are limited reports of patients experiencing significant improvement of their symptoms following a thymectomy. We report on 2 patients with SPS who underwent thymectomies at our institution. CASE PRESENTATION: A 39-year-old lady presented with frequent falls associated with lower back pain and stiffness of her lower limbs which led to difficulties with ambulation. A diagnosis of SPS was made based on her symptoms, an electromyogram (EMG) showing continuous motor unit activity and elevated anti-glutamic acid decarboxylase (GAD) antibody levels. Computed tomography (CT) scan of the thorax revealed a large well-circumscribed mediastinal mass (Fig.1 and 2), which was confirmed to be a thymoma after percutaneous biopsy. She underwent surgical resection of the mass and histopathology revealed a Modified Masaoka Stage IIa type B1 thymoma. Post operatively, she made an uneventful recovery and was able to ambulate independently with a walking frame on discharge. Our second patient was a 54-year-old ophthalmologist who presented with intermittent episodes of myoclonic jerks of her trunk, worsened by stress and auditory or tactile stimuli with elevated anti-GAD antibody levels. CT thorax revealed a hyperdense heterogeneity in the anterior superior mediastinal region. She underwent surgery and histopathology showed thymic tissue with reactive lymphoid hyperplasia. Her symptoms improved post-operatively and she was able to resume work. DISCUSSION: SPS associated with thymic abnormalities occurs more frequently in females (66%), and mean age of diagnosis was 55 years. Currently, there are 7 reported cases worldwide of SPS associated with thymoma, with patients reporting a significant improvement of symptoms following thymectomy. Most were World Health Organisation (WHO) type B1/B2 thymomas, with one AB and one invasive carcinoma. Five of the 7 cases had elevated anti-GAD antibody levels, which dropped significantly post-thymectomy. Symptom recurrence occurred spontaneously or following tactile stimuli in 3 of these cases. This was successfully controlled with pyridostigmine, intravenous immunoglobulin (IVIG) or plasmapheresis. All patients remained symptom free on long term follow up. CONCLUSIONS: In conclusion, limited reports suggest that thymectomy can be effective for relieving symptoms of SPS and should be strongly considered when thymomas are discovered in association with this condition. However, all patients should be counselled that symptoms may recur in future and thus remain on long-term follow up with a neurologist. Reference #1: Solimena M, Folli F, Denis-Donini S, Comi GC, Pozza G, De Camilli P, Vicari AM: Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus. N England J Med. 1988, 318:1012-20. 10.1056/NEJM198804213181602 Reference #2: Gershanik OS: Stiff-person syndrome. Parkinsonism Relat Disord. 2009, 15:S130-S134. 10.1016/S1353-8020(09)70799-0 DISCLOSURE: The following authors have nothing to disclose: Rachel Chen Yanlin, Tousif Kabir, Atasha Asmat, Dokev Basheer Ahmed Aneez No Product/Research Disclosure Information

Seropositive PERM associated with leucocytoclastic vasculitis

Background: Progressive encephalomyelitis, rigidity, and myoclonus (PERM) is a variant stiff-person plus syndrome consisting of brainstem and pyrimidal dysfunction, muscular rigidity, stimulus-evoked spasms, and dysautonomia. Continuous motor-unit activity from ectopic anterior horn cell discharges underlies the myotomal hyperactivity. Case Report: A 51-year-old man with an 8-year history of “spasmodic” mid and low back pain presented with increasing stiffness, hyperekplexia-induced opisthotonus-like posturing, urinary retention, long-tract motor signs, and diplopia. He had a recent history of biopsy-confirmed leucocytoclastic vasculitis-associated diffuse maculopapular rash. He responded well to IVIg treatment manifested by improved 1) gait fluidity, 2) bowel and bladder function 3) tolerance to startle, and 4) vision. Results: Serological testing revealed positive anti-glycine receptor antibodies. Anti-glutamic acid decarboxylase and voltage-gated K+-channel antibodies were absent. A chest CT was unremarkable. Conclusions: This is the second case of seropositive PERM in Canada and the first associated with leucocytoclastic vasculitis. Pathologic findings in PERM reveal perivascular lymphocytic cuffing in the rhombencephalon and spinal cord. Glycine receptor localization correlates with neurologic dysfunction. Mid-brain involvement may underlie the autonomic dysfunction but evidence of direct glycinergic inhibition of the external urethral sphincter in Onuf’s nucleus may be responsible for urinary retention.

An Unusual Cause of Swan Neck Deformity of the Fingers

To describe a patient who presented with nonfixed swan neck deformity of the fingers and generalized body aches. Case report. Tertiary care teaching hospital. A 38-year-old woman who presented with swan neck deformity of the fingers. Electromyographic finding and electromyographic and clinical response to intravenous immunoglobulin. Needle electromyography revealed continuous motor unit activity in the 50- to 70-Hz frequency during the resting state for all the muscles sampled, which suggests the possibility of neuromyotonia. After ruling out possible secondary causes, we treated the patient with intravenous immunoglobulin, considering primary neuromyotonia. The body ache improved by 100% on the visual analogue scale, and the electromyographic discharges disappeared from the paraspinal and tibialis anterior muscles and changed in its morphology to doublets, triplets, and multiplets in the first dorsal interossei and flexor digitorum profundus. Neuromyotonia should be considered in the differential diagnosis of swan neck deformity of the fingers, especially in cases that show no fixed deformity and are not associated with any other rheumatologic stigmata.

Cannabis derivatives therapy for a seronegative stiff-person syndrome: a case report

Stiff-person syndrome (SPS) is an uncommon and disabling disorder characterized by progressive rigidity and episodic painful spasms involving axial and limb musculature. SPS treatment is mostly based on benzodiazepines, baclofen, immunosuppressants and intravenous immunoglobulin. Cannabis derivatives [tetrahydrocannabinol (THC) and cannabidiol (CBD)] are available as an oromucosal spray (Sativex(®)), indicated as add-on treatment, for symptom improvement in patients with moderate to severe spasticity because of multiple sclerosis (MS). Our objective is to report a case of seronegative SPS successfully treated with THC-CBD oromucosal spray. We report a case of a 40-year-old man presenting with progressive muscle stiffness and intermittent spasms for 6-years. The diagnosis of stiff-person syndrome was based on the clinical features and neuroelectrophysiologic findings of continuous motor unit activity. Glutamic acid decarboxylase autoantibodies was absent in our patient, in both serum and cerebrospinal fluid (CSF). Cannabis derivatives oromucosal spray was introduced after a series of unsatisfactory traditional medical treatments. After 14 months treated with THC-CBD oromucosal spray, improvement was verified in the eight dimensions of the scale of SF-36 quality of life questionnaire. Clinical experience with cannabis derivatives in patients with multiple sclerosis is accumulating steadily, but there is no current literature about its efficacy for SPS. Because MS and SPS share some neurological symptoms such as spasticity and rigidity, it is thought that THC-CBC can be an option for SPS patient. Our case report suggests that THC-CBD oromucosal spray is an alternative treatment for patients with refractory SPS, and further validation is appropriate.

Electrophysiological characteristics in four patients from Brazil with stiff person syndrome

Stiff person syndrome (SPS) is a rare immune-mediated disorder of the central nervous system characterized by muscle rigidity and episodic muscle spasms. The diagnosis of SPS is based on electrophysiological studies. We analyzed the electrophysiological features in four patients from Brazil who fulfilled the clinical criteria for SPS. The most common electrophysiological abnormalities were continuous motor unit activity, co-contracting, and the presence of the cutaneomuscular reflex. Despite all patients having clinical characteristics of SPS during the disease, no patient met all the electrophysiological criteria for SPS even after repeat electrophysiological studies. This shows that a diagnosis of SPS should not be restricted to patients with all the classic electrophysiological changes but should be considered in the presence of one or some of those changes.

Sıra Dışı Bir Hastalıkta Terapötik Plazma Değişimi: Stiff-Person Sendromu

Stiff-Person syndrome (SPS) is a rare and disabling disorder characterized by continuous motor unit activity causing severe rigidity and episodic spasms in axial and limb muscles. It deteriorates the quality of life and causes a serious burden in the patient’s life. It is frequently associated with other autoimmune diseases such as diabetes mellitus. Treatment with intravenous immunoglobulin, anti-anxiety drugs, muscle relaxants, anti-convulsants will improve symptoms, but will not cure the disorder. Therapeutic plasma exchange is an alternative treatment for the patients resistant to other treatment options. Here, we report a patient with SPS treated in intensive care unit and underwent therapeutic plasma exchange.

Efficacy of pregabalin in a case of stiff-person syndrome: Clinical and neurophysiological evidence

Symptomatic treatment of stiff-person syndrome (SPS) might be challenging and a significant improvement of stiffness and rigidity is generally reached with high doses of benzodiazepines or baclofen causing side effects.A 71-year old woman diagnosed with SPS complained of marked stiffness of trunk and lower limb muscles with sudden painful spasms. She was unable to walk and she could not lean on her right leg. Cortical silent period (CSP) duration evaluated from right abductor pollicis brevis (APB) with transcranial magnetic stimulation was shortened. Polygraphic electromyographic (EMG) evaluation from paraspinal and leg muscles disclosed continuous motor unit activity at rest with interference muscular pattern. Symptomatic treatment with diazepam was withdrawn because of excessive sedation. In order to relieve the intense lumbar pain, she was prescribed pregabalin; since the day after, rigidity and painful spasms dramatically improved and she could walk without assistance. The clinical benefit persisted at 3months follow-up and was paralleled by almost complete disappearance of EMG activity at rest and prolongation of CSP. The clinical and electrophysiological data in this SPS patient suggest the possible efficacy of pregabalin as symptomatic treatment without any significant side effects, which needs to be replicated in larger case series.

A Novel Movement Disorder in Related Male Labrador Retrievers Characterized by Extreme Generalized Muscular Stiffness

To describe the clinical phenotype of a new motor disorder in Labrador Retrievers. Case series study. Seven young male Labrador Retrievers presented for evaluation of stiff gait. All affected dogs had generalized muscular stiffness, persistent at rest and resulting in restricted joint movements. They showed a forward flexed posture, festinating gait, and bradykinesia. Signs developed between 2 and 16 months of age and tended to stabilize in adulthood. Needle electromyogram in the conscious state showed continuous motor unit activity in resting epaxial and proximal limb muscles. This activity was abolished by general anesthesia. Muscle and nerve histopathology was normal. In 2 dogs necropsied, astrocytosis was evident throughout the spinal cord gray matter, reticular formation and caudate nuclei. Decreased neuronal counts were selectively found in the spinal cord Rexed's lamina VII, but not in VIII and IX. Pedigree analysis showed that the affected dogs were from 5 related litters. This new hypertonicity syndrome in Labrador Retrievers is unique because of the selective distribution of the histological lesions, the lack of progression in adulthood, and its exclusive occurrence in male dogs. Pedigree analysis suggests an X-linked hereditary disease, although other modes of inheritance cannot be ruled out with certainty. We hypothesize that altered output from basal nuclei and reticular formation together with motor neuron disinhibition caused by a decreased number of spinal cord interneurons leads to the muscular stiffness.

A case of glycine-receptor antibody-associated encephalomyelitis with rigidity and myoclonus (PERM): clinical course, treatment and CSF findings

Over several months a 58-year-old man developed muscle stiffness, myoclonus and experienced several sudden falls caused by sensory and acoustic stimuli. On neurological examination, a severe startle reaction could be triggered by unexpected noises and there was stiffness, especially of the back and lower limb muscles, with myoclonus, lower limb paraparesis, muscle rigidity and increased tendon reflexes without further pyramidal signs. He was not able to walk without help. He also exhibited a mild pontine syndrome with disturbed smooth pursuit eye movements and diplopia. Electrophysiological studies revealed ubiquitous early recruitment and continuous motor unit activity as described for stiff person syndrome by Meinck and Thompson [1]. Cerebral MRI scans were normal. Antibodies against glutamic acid decarboxylase (GAD), amphiphysin, CYFRA 21-1, CEA, Ri, Hu, Yo, MA1, MA2, CV2 and CRMP5 could not be detected in serum. Neuron-specific enolase (NSE) enzyme concentrations were not raised. An extensive cancer search including 18-F-FDG-PET, abdominal ultrasound, X-ray of the chest and bronchoscopy was negative. However, serum glycine receptor (GlyR) antibodies were detected by a cell-based assay (Fig. 1) [2]. Initial lumbar puncture revealed oligoclonal IgG bands and 45 lymphocytes/ll (normal: \4 cells/ll) in the cerebrospinal fluid (CSF). GlyR antibodies could also be found in the patient’s CSF. Gamma-aminobutyric acid (GABA) and glutamate levels in CSF were measured by HPLC, with electrochemical detection after precolumn o-phthaldialdehyde sulphite derivatization, in the patient’s CSF and control samples from 10 subjects (4 males, 6 females); age range 35–83 years (mean 54 years) undergoing diagnostic lumbar puncture as part of their investigations. Their CSF analyses were normal and neurological disorders were excluded. All lumbar punctures were done between 11.00 am and 2.00 pm. Their GABA levels were 42.7 ± 14.2 nmol/l. As shown in Fig. 2, before any treatment the patient’s GABA level was higher (89.0 nmol/l) than upper limit of the control range (mean ? 3SDs, 85.3 nmol/l). Glutamate levels were also lower (initial: 0.33 lmol/l; after 18 months: 0.35 lmol/l) than controls (0.49 ± 0.2 lmol/l) although not significantly different. The neurological symptoms ameliorated after an initial therapy of six plasmaphereses followed by oral corticosteroids (1 mg/kg body weight). The GABAA receptor agonist clonazepam led to a further improvement of muscle stiffness and rigidity. Only a mild pontine symptom with diplopia persisted. CSF GABA levels fell over the treatment period to 28.5 nmol/l (18 months after initial lumbar puncture). GlyR antibody titers also declined but were still just detectable in the serum at 12 months (Fig. 1). Once the improvement had stabilised for 18 months, we tried to wean the steroids. After 2 weeks without steroids the patient developed again neurological symptoms with a left internuclear ophthalmoplegia, and without signs on the MRI. Steroids were therefore increased to 0.5 mg/kg and a steroidsparing drug, azathioprine (2 mg/kg), was introduced. Under this regime the patient is now without symptoms. Up to now, medical examinations are being done every 6 months. A. Piotrowicz (&) A. Thumen A. Moser Neurochemical Research Group, Department of Neurology, University of Lubeck, Ratzeburger Allee 160, 23538 Lubeck, Germany e-mail: agnieszka.piotrowicz@neuro.uni-luebeck.de

Stiff-Person Syndrome Following Tick-Borne Meningoencephalitis

Stiff-person syndrome (SPS) is a rare disorder characterized by muscle stiffness and painful spasms. Misdiagnosis may occur due to the fact that the clinical picture of SPS is often atypical. The main pathophysiologic mechanism underlying the development of SPS is insufficient inhibition at the cortical and spinal levels. There is good evidence for a primary autoimmune etiology. A 61-year-old man was admitted to a neurological department due to muscle hypertonia with episodic attacks of painful spasms predominantly affecting axial muscles. The symptoms developed shortly after tickborne meningoencephalitis. Electromyography (EMG) revealed signs of continuous motor unit activity. Antibodies against glutamate decarboxylase (anti-GAD) were highly elevated. We present a case of a man who developed clinically severe anti-GAD positive SPS, provoked by tick-borne encephalitis. After therapeutic plasma exchange (TPE) a rapid, temporary improvement of the clinical and neurophysiological findings was noted. Only after being placed on long-term immunosuppression did the patient achieve stable recovery. This case supports the importance of EMG findings and demonstrates the effect of TPE as well as the need for chronic immunosuppression in severe cases of SPS.