暂无摘要。

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is part of the variant type of the Stiff Person Syndrome (SPS) and is a rare neurological disease. We report here a patient with PERM who had thymoma and was positive for anti-glutamic acid decarboxylase (anti-GAD) antibodies. Her symptoms improved after treatment with hormones and gamma globulin. We also summarized the literature review of patients with PERM accompanied by tumors reported.

OBJECTIVE: To report a case of sudden onset vertical diplopia, blurred vision, and muscle spasms.
METHODS: This is a case report of a 57-year-old female who presented to the accident and emergency department with a one day history of vertical diplopia and a two week history of lower limb spasticity secondary to muscle spasms.
RESULTS: The patient had no significant medical or ocular history. Orthoptic investigation initially revealed a left inferior rectus (IR) underaction. Possible diagnoses at this point were thought to be isolated IR weakness, myasthenia gravis or skew deviation. An urgent MRI scan was arranged and blood tests were taken. MRI showed no abnormalities. Blood tests were normal, however, the acetylcholine receptor antibody serum test (ACH-R) was 0.43 nmol/L, which is at the high end of normal. At the follow-up visit, the IR weakness had deteriorated and the patient had also developed gaze-evoked nystagmus. An appointment with the neurologist and neuro-ophthalmologist was expedited. When the patient returned, she reported that her neurologist had diagnosed her with stiff-person syndrome (SPS). The patient had also developed a laterally alternating skew deviation and reported that she had undergone a course of intravenous immunoglobulin (IVIG). The patient was prescribed diazepam and gabapentin. Due to the lack of recovery, persistent diplopia and oscillopsia, monthly IVIG have been prescribed.
CONCLUSIONS: There is currently a paucity of literature relating to ophthalmic problems with SPS and how they are best treated. Previous reports have established that there is a link with myasthenia gravis, with many patients going on to develop myasthenia. Treatment of SPS is lacking large evidence-based studies. However, treatment with muscle relaxants and anticonvulsants has provided a good outcome for some. Further research is required to develop an evidence-based approach to treating the ophthalmological problems patients with SPS experience. This case report highlights the importance and value of orthoptists in investigating and monitoring patients with stiff-person syndrome.

暂无摘要。

The clinical spectrum of anti-glutamic acid decarboxylase (GAD) antibody-associated neurologic syndromes is expanding, with focal, generalized, and atypical forms.
We describe a 59-year-old female showing continuous right lower limb myoclonus and mild encephalopathy. These symptoms started 2 weeks prior to evaluation. The patient had great improvement with intravenous steroids. An autoantibody panel was positive for anti-GAD.
Various clinical manifestations, including myoclonus, may relate to anti-GAD antibodies. The treatment options available include symptomatic drugs, intravenous immunoglobulin, steroids, and other immunosuppressant agents.

BACKGROUND: Anti-glutamic acid decarboxylase (anti-GAD65) antibodies are a rare cause of autoimmune encephalitis. This entity is mainly recognized in adults and very few cases were reported in children. We report on a paediatric case of anti-GAD encephalitis with severe presentation and uncontrollable dysautonomia.
METHODS: A 9-year-old girl was referred to our department for refractory seizures and behavioral disturbances. Brain magnetic resonance imaging (MRI) was normal. Repeat screening for antineuronal antibodies showed negative results for anti-NMDA receptor antibodies but positive results for anti-GAD65 with a low positivity of anti-Ma2 antibodies. Although a transient improvement was noticed after immunomodulatory treatment, the patient developed severe intractable autonomic imbalance including dysrythmia, alternating bradycardia/tachycardia, hypotension/hypertension, hypothermia/hyperthermia and hyperhidrosis. She deceased six months after onset.
CONCLUSIONS: Our report intends to raise awareness of autoimmune encephalitis with anti-GAD65 antibodies which may involve extralimbic brain regions and manifest with fatal dysautonomia. We highlight the need for prompt diagnosis and aggressive management for this underdiagnosed entity in children.

Antibodies to glutamic acid decarboxylase (GAD-Abs) have been associated with several conditions, rarely involving the autonomic nervous system. Here, we describe two patients complaining of autonomic symptoms in whom a post-ganglionic autonomic neuropathy has been demonstrated in association with significantly elevated serum and CSF GAD-Abs levels.
Patients underwent nerve conduction studies, sympathetic skin response testing, evaluation of autonomic control of the cardiovascular system and skin biopsy. Also, serum screening to exclude predisposing causes of peripheral neuropathy was performed. Anti-GAD65 antibodies were evaluated in serum and CSF.
GAD-Abs titer was increased in both serum and CSF in both patients. Sympathetic skin response was absent and skin biopsy revealed a non-length-dependent small-fiber neuropathy with sympathetic cholinergic and adrenergic post-ganglionic damage in both patients. Nerve conduction studies and evaluation of autonomic control of the cardiovascular system were normal in both patients. Both patients were treated with steroids with good, but partial, (patient 2) recovery of the autonomic dysfunctions.
Although the pathophysiological mechanisms involved are not fully defined, GAD-abs positivity in serum and CSF should be searched in patients with autonomic neuropathy when no other acquired causes are evident. This positivity may help to clarify autoimmune etiology and, subsequently, to consider immunomodulatory treatment.

BACKGROUND: \"Classic\" stiff person syndrome (SPS) features stiffness, anti-glutamic acid decarboxylase (anti-GAD) antibodies, and other findings. Anti-GAD antibodies are also detected in some neurological syndromes (such as ataxia) in which stiffness is inconsistently present. Patients with otherwise \"classic\" SPS may either lack anti-GAD antibodies or be seropositive for others. Hence, SPS cases appear to fall within a clinical spectrum that includes conditions such as progressive encephalomyelitis with rigidity and myoclonus (PERM), which exhibits brainstem and autonomic features. We have compiled herein SPS-spectrum cases reported since 2010, and have segregated them on the basis of likely disease mechanism (autoimmune, paraneoplastic, or cryptogenic) for analysis.
METHODS: The phrases \"stiff person syndrome\", \"PERM\", \"anti-GAD antibody syndrome\", and \"glycine receptor antibody neurological disorders\" were searched for in PubMed in January 2015. The results were narrowed to 72 citations after excluding non-English and duplicate reports. Clinical descriptions, laboratory data, management, and outcomes were categorized, tabulated, and analyzed.
RESULTS: Sixty-nine autoimmune, 19 paraneoplastic, and 13 cryptogenic SPS-spectrum cases were identified. SPS was the predominant diagnosis among the groups. Roughly two-thirds of autoimmune and paraneoplastic cases were female. Anti-GAD antibodies were most frequently identified, followed by anti-amphiphysin among paraneoplastic cases and by anti-glycine receptor antibodies among autoimmune cases. Benzodiazepines were the most commonly used medications. Prognosis seemed best for cryptogenic cases; malignancy worsened that of paraneoplastic cases.
CONCLUSIONS: Grouping SPS-spectrum cases by pathophysiology provided insights into work-up, treatment, and prognosis. Ample phenotypic and serologic variations are present within the categories. Ruling out malignancy and autoimmunity is appropriate for suspected SPS-spectrum cases.

BACKGROUND: Anti-glutamic acid decarboxylase antibodies are associated with encephalopathy, an autoimmune central nervous system inflammatory disease. The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)+49 A/G polymorphism has been shown to confer genetic susceptibility to positive anti-glutamic acid decarboxylase antibodies in patients with type 1 diabetes mellitus in Japan. We aimed to investigate the association of the CTLA-4+49 A/G (rs231775) polymorphism in Taiwanese children with anti-glutamic acid decarboxylase antibody-associated encephalopathy.
METHODS: This was a case-control study from July 2011 to June 2012 performed at Chang Gung Children\'s Hospital in Taiwan. Genotyping of the CTLA-4+49 A/G polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism.
RESULTS: Seventeen patients with anti-glutamic acid decarboxylase antibody-associated encephalopathy and 97 controls were enrolled. The genotype, allele and carrier frequencies of the CTLA-4+49 A/G polymorphism were equally distributed in the patients and controls, with no significant differences between the two groups. In addition, we found a positive trend between the level of anti-glutamic acid decarboxylase antibodies and the G allele of the CTLA-4+49 A/G polymorphism, although this trend was not statistically significant.
CONCLUSIONS: Our results suggest that the CTLA-4+49 A/G (rs231775) polymorphism does not confer an increased susceptibility to anti-glutamic acid decarboxylase antibody-associated encephalopathy in Taiwanese children.

BACKGROUND: There have been inconsistent reports on the potential association between diabetes mellitus and epilepsy.
METHODS: We examined a consecutive cohort of 2016 people with pharmacoresistant epilepsy admitted to a tertiary medical centre.
RESULTS: We identified 20 individuals with type 1 diabetes mellitus (T1DM); a point prevalence of 9.9 (95% CI: 6.4, 15.3) cases per 1000 individuals. This represents a more than two-fold increase relative to published prevalence estimates of T1DM in the general population. The onset of T1DM preceded that of epilepsy in 80% of individuals, by a median of 1.5 years. Individuals with T1DM were significantly more likely to have cryptogenic/unknown epilepsy relative to those with type 2 diabetes mellitus or without diabetes (85% versus 35% and 49%, p=0.045). All individuals with T1DM had focal epilepsy, the majority of which were temporal lobe in origin, although there was no evidence that this proportion was any different from those without T1DM (p>0.999).
CONCLUSIONS: The prevalence of T1DM appears to be increased in people with pharmacoresistant epilepsy and is associated with cryptogenic/unknown epilepsy. These findings may have pathophysiological implications, especially in the context of anti-glutamic acid decarboxylase antibodies.