The case of a 30-year-old man with subacute gait instability, weakness, and muscle spasms.

A 30-year-old healthy man presents after a fall with diffuse weakness and pain and recent onset left eye ptosis in the setting of three weeks of progressive bilateral leg weakness, gait instability, and difficulty washing his hair due to upper extremity weakness. He had also developed stiffness in his neck and shoulders and uncontrollable muscle spasms. Exam was notable for ptosis, fatiguing weakness in extremities, increased tone, hyperreflexia with clonus, and spastic gait. A mediastinal mass was found on chest CT (Fig. 1), and biopsy confirmed an invasive thymoma with positive nodes. Serum testing was positive for antibodies to acetylcholine receptors as well as glutamic acid decarboxylase.

Anti-glutamic acid decarboxylase (GAD) positive cerebellar Ataxia with transitioning to progressive encephalomyelitis with rigidity and myoclonus (PERM), responsive to immunotherapy: A case report and review of literature.

We present a case of a 65-year-old African American male, immunosuppressed on Tacrolimus, who initially presented with cerebellar ataxia and rapidly developed Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM) with positive anti-glutamic acid decarboxylase (GAD65) antibodies, no underlying malignancy, and normal neuroimaging. PERM is a rare spectrum of Stiff Person Syndrome (SPS), which is strongly associated with anti-GAD antibodies and characterized by flare-ups and remissions of encephalopathy, myelopathy and rigidity with myoclonus. PERM is diagnosed clinically and has been successfully treated with both Intravenous Immunoglobulin (IVIg) and plasmapheresis. Our patient was successfully treated with IVIg. On day 14 after starting IVIg treatment, his neurological symptoms started to improve and ultimately returned to baseline.

The neurological syndromes associated with glutamic acid decarboxylase antibodies.

A number of neurological syndromes have been described in patients with positive serum antibodies (Abs) against the enzyme glutamic acid decarboxylase (GAD), the rate limiting step in the synthesis of GABA (γ-aminobutyric acid). These disorders include: classical stiff-person syndrome and variants, cerebellar ataxia, limbic and extra-limbic encephalitis, nystagmus/oculomotor dysfunction, drug-resistant epilepsy, paraneoplastic stiff-person syndrome and progressive encephalopathy with rigidity and myoclonus (PERM), the latter two are mainly related to amphiphysin and the glycine receptor Abs respectively; but patients may also have positive GAD-Abs. Although observations are consistent with an autoimmune response in these patients and there is evidence of GABAergic dysfunction in some cases; the pathogenic role of GAD-Abs in the nervous system has not been clarified and it is a matter of debate. The diagnosis of these syndromes is based on clinical grounds plus the presence of GAD-Abs in serum and CSF with demonstration of intrathecal secretion. Although some presentations may be negative for GAD-Abs, such as stiff-person syndrome; positive GAD-Abs are required for the diagnosis in patients with cerebellar ataxia, encephalitis, and epilepsy. Immunotherapy is required for most patients. Intravenous immunoglobulins, oral or IV steroids and plasma exchange are considered the first line options, aimed to induce remission, but chronic immunosuppression is usually required. Symptomatic therapy should also be provided, aimed to control muscle spasms, seizures, delirium, etc. Prognosis varies among patients; but it is considered intermediate between that of patients with neurological syndromes associated with neural Abs against membrane antigens and those with onconeural Abs.

Open-label trial of ranolazine for the treatment of paramyotonia congenita.

INTRODUCTION: Paramyotonia congenita (PMC) is a nondystrophic myotonic disorder that is believed to be caused by a defect in Nav 1.4 sodium channel inactivation. Ranolazine, which acts by enhancing slow inactivation of sodium channels, has been proposed as a therapeutic option, but in vivo studies are lacking. METHODS: We conducted an open-label, single-center trial of ranolazine to evaluate efficacy and tolerability in patients with PMC. Subjective symptoms of stiffness, weakness, and pain as well as clinical and electrical myotonia were evaluated. Baseline measures were compared with those after 4 weeks of treatment with ranolazine. RESULTS: Ranolazine was tolerated well without any serious adverse events. Both subjective symptoms and clinical myotonia were significantly improved. Duration of myotonia was reduced according to electromyography, but this change was not statistically significant in all tested muscles. DISCUSSION: Our findings support the use of ranolazine as a treatment for myotonia in PMC and suggest that a randomized, placebo-controlled trial is warranted. Muscle Nerve 59:240-243, 2019.

Anaesthetic management of a patient with a unique combination of anti-N-methyl-D-aspartate receptor encephalitis and stiff-person syndrome.

Stiff-person syndrome (SPS) and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis are rare paraneoplastic syndromes caused by antibodies that target the central nervous system. Here, we describe a 26-year-old woman who presented with psychosis, amnesia, rigidity and fever. After extensive diagnostic and laboratory workup, she was diagnosed with an ovarian teratoma which was causing the symptoms of anti-NMDAR encephalitis and SPS. The patient was successfully treated with laparoscopic removal of the ovarian tumour under general anaesthesia. She was placed on immunosuppressant medications preoperatively and postoperatively, and her symptoms gradually resolved. Although there are case reports regarding the anaesthetic management of SPS and anti-NMDAR encephalitis, our study is the first report of a patient afflicted with both conditions.

Paraneoplastic stiff person syndrome: Inpatient rehabilitation outcomes of a rare disease from two cancer rehabilitation programmes.

Paraneoplastic stiff person syndrome is a rare, but debilitating, manifestation of cancer, characterized by painful extremities, truncal and facial spasms. The resultant functional impairment may necessitate comprehensive rehabilitation and symptom management. This case series describes the acute inpatient rehabilitation courses of 2 patients at different tertiary care referral cancer rehabilitation programmes, including work-up and diagnosis, medical management of symptoms, and functional outcomes. Both patients had a reduction in symptom burden and an improvement in motor function as a result of multidisciplinary acute inpatient rehabilitation.

A Rare Case of Childhood Stiff Person Syndrome Associated With Pleuropulmonary Blastoma.

INTRODUCTION: Stiff person syndrome is a rare autoimmune, neurological disorder characterized by progressive rigidity and episodic painful spasms, predominantly affecting the proximal limbs and axial muscles, and leading to progressive disability. We report the case of a child who developed symptoms compatible with stiff person syndrome during treatment for pleuropulmonary blastoma. PATIENT DESCRIPTION: A 3-year, 5-month-old girl was admitted for gradually worsening postural tremor, painful spasms, and generalized stiffness. Since the age of 3 years, she had been on adjuvant chemotherapy for pleuropulmonary blastoma before surgical resection. Brain magnetic resonance imaging and electroencephalographic findings were normal. Although serologic tests for autoimmune disease, including paraneoplastic antibodies and antiglutamic acid decarboxylase antibodies, were unremarkable, her findings were attributed to a paraneoplastic syndrome based on her clinical features and medical history. However, following the planned pulmonary lobectomy, her symptoms were paradoxically aggravated, with continuous motor unit potential at rest on electromyography, which occurs in stiff person syndrome. She gradually improved during postadjuvant chemotherapy with simultaneous immunotherapy including intravenous immunoglobulins and methylprednisolone, and she had recovered completely when evaluated at the 22-month follow-up visit after completion of her treatment for pleuropulmonary blastoma. CONCLUSION: We present the first documented child with stiff person syndrome associated with pleuropulmonary blastoma. The marked clinical improvement following chemotherapy for pleuropulmonary blastoma was yet more proof of the pleuropulmonary blastoma-related stiff person syndrome. In children with a malignancy and stiff person syndrome, a paraneoplastic syndrome should be considered and the treatment for the malignancy must be undertaken.

Apraxia in anti-glutamic acid decarboxylase-associated stiff person syndrome: link to corticobasal degeneration?

Corticobasal syndrome (CBS) is associated with asymmetrical rigidity as well as asymmetrical limb-kinetic and ideomotor apraxia. Stiff person syndrome (SPS) is characterized by muscle stiffness and gait difficulties. Whereas patients with CBS have several forms of pathology, many patients with SPS have glutamic acid decarboxylase antibodies (GAD-ab), but these 2 disorders have not been reported to coexist. We report 2 patients with GAD-ab-positive SPS who also had signs suggestive of CBS, including asymmetrical limb rigidity associated with both asymmetrical limb-kinetic and ideomotor apraxia. Future studies should evaluate patients with CBS for GAD-ab and people with SPS for signs of CBS.

Stiff-person syndrome: insights into a complex autoimmune disorder.

Stiff-person syndrome (SPS) is characterised by progressive rigidity and muscle spasms affecting the axial and limb muscles. Since its initial description in 1956, marked progress has been made in the clinical characterisation, understanding of pathogenesis and therapy of this disorder. SPS can be classified according to the clinical presentation into classic SPS and SPS variants: focal or segmental-SPS, jerking-SPS and progressive encephalomyelitis with rigidity and myoclonus. Most patients with SPS have antibodies directed against the glutamic acid decarboxylase, the rate-limiting enzyme for the production of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Antibodies directed against GABA(A) receptor-associated protein, and the glycine-α1 receptor can also be observed. Paraneoplastic SPS is commonly associated with antiamphiphysin antibodies and breast cancer. Treatment of SPS with drugs that increase the GABAergic tone combined with immunotherapy can improve the neurological manifestations of these patients. The prognosis, however, is unpredictable and spontaneous remissions are unlikely.

Stiff person syndrome: a case report.

The case report features a patient who had a diagnosis of a common type of breast cancer with an uncommon neurologic syndrome. She had extreme pain and progressive stiffness with cognitive and functional decline. This article includes the pathogenesis and treatment options for a rare, but treatable, autoimmune disorder of malignancy called stiff person syndrome.

Non-stiff anti-amphiphysin syndrome: clinical manifestations and outcome after immunotherapy.

Amphiphysin antibody causes paraneoplastic stiff-person syndrome and can also result in a variety of neurological manifestations. Here, we investigated the clinical spectrum of 20 patients with non-stiff anti-amphiphysin syndrome and their responses to immunotherapy. The most common neurological manifestation was limbic encephalitis (n=10), followed by dysautonomia (n=9), and cerebellar dysfunction (n=6). Cancer was detected in only seven patients. Intravenous immunoglobulin or steroid treatment was effective in most patients, but three improved only after rituximab treatment. Our study suggests that anti-amphiphysin syndrome can manifest as non-stiff encephalomyelitis and is only partially associated with cancer. Active immunotherapy, including rituximab, would be beneficial.

Infantile spasms and hyperekplexia associated with isolated sulfite oxidase deficiency.

IMPORTANCE: Isolated sulfite oxidase deficiency (ISOD) causes severe intellectual disability, epilepsy, and shortened life expectancy. Intractable seizures are invariable in children with ISOD; however, to our knowledge, infantile spasms with a corresponding hypsarrhythmia pattern on electroencephalogram have never been reported. In addition, the nonepileptic paroxysmal movement disorder hyperekplexia has not previously been reported with ISOD. OBSERVATIONS: We describe an infant with ISOD who initially presented with neonatal seizures, diffusion restriction noted on magnetic resonance imaging, and elevated serum S-sulfocysteine consistent with ISOD. A homozygous mutation in the SUOX gene was identified, confirming the diagnosis. Uniquely, this patient developed a profound accentuated startle response that did not have a corresponding electrographic change on electroencephalogram consistent with hyperekplexia. This was followed by a change in the child's electroencephalogram to the chaotic pattern of hypsarrhythmia and brief tonic seizures with attenuation of the hypsarrhythmia pattern characteristic of infantile spasms. CONCLUSIONS AND RELEVANCE: The evolution of seizures associated with ISOD is poorly characterized because of the small number of patients. We report what we believe to be the first case of a child with ISOD who developed infantile spasms and hyperekplexia. This expands the phenotypes associated with ISOD and also should caution clinicians to not assume that all abnormal movements are seizures.

Patterns of decline in upper limb function of boys and men with DMD: an international survey.

With increasing life expectancy, upper extremity (UE) function becomes more and more important in boys with Duchenne muscular dystrophy (DMD). Knowledge of UE function in these children is, however, limited. The aim of this study was to gain insight into the changing patterns of UE function during the course of DMD. A Web-based questionnaire on UE function, covering all domains of the International Classification of Functioning Disability and Health, was distributed worldwide. Primary domains of the questionnaire were: participant characteristics, UE pain and stiffness, UE activities, and social participation. Data were described per disease stage and analyzed using descriptive analysis. A total of 213 boys/men with DMD (1-35 years) were included in this study. UE pain, stiffness, and activity limitations increased with disease stage. UE activity limitations already occurred in the early ambulatory stage. Compared to the healthy population, social participation was restricted in DMD patients and about 70% of the respondents experienced UE limitations when performing social activities. Despite the existence of UE impairments, only 9% of the respondents used supportive aids. Functional capacities and activities of the UE are limited already in the early ambulatory stage of patients with DMD affecting their social participation. Therefore, clinicians should pay attention to UE limitations before DMD patients lose their capacity to walk. Effective and adequate aids as well as attention for pain and stiffness in the therapeutic management could help to reduce UE activity limitations and related restrictions in social participation.

The horses are the first thought but one must not forget the zebras even if they are rare: Stiff person syndrome associated with malignant mesothelioma.

Stiff person syndrome (SPS) is a rare condition that causes rigidity in the muscles of the body and extremities, difficulty in walking, episodic spasms and progressive disability. SPS is generally seen together with autoimmune disorders such as diabetes mellitus, thyroiditis, vitiligo and pernicious anaemia. Rarely, it may develop as a paraneoplastic condition. SPS cases associated with breast cancer, small cell lung carcinoma, thymoma, Hodgkin's lymphoma and colorectal cancer have been reported in the literature. We present a case of a 58-year-old female patient who had malignant mesothelioma-associated SPS. Patients who have muscle spasms and difficulty in movement of joints should be evaluated for SPS before diagnosis of Parkinson's or other neurological disorders, and possible underlying malignancies should be excluded.

Stiff man syndrome with invasive thymic carcinoma.

Stiff man syndrome is a rare disease characterized by painful chronic spasms in the muscle and skeletal system. This syndrome is an autoimmune neurologic disorder which is associated with thymoma. We treated a 32-year-old male patient with a type C thymoma (based on the World Health Organization classification) who had stiff man syndrome. The patient underwent an extended thymectomy which brought about alleviation of his symptoms.