RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Licorice preparations are used as neuroprotective remedies in Persian ethnomedicine, in order to prevent from disabilities in neurodegenerative conditions like Parkinson's disease (PD). AIM OF THE STUDY: This study was designed to determine the licorice (root of Glycyrrhiza glabra L.) effectiveness as an adjunct treatment in the PD management. MATERIAL AND METHODS: In this double-blinded trial, 128 patients were assessed for eligibility criteria. Seventy-eight patients were ineligible and 11 of them refused from participating. Thirty-nine PD patients (YAHR stagingâ¯≤â¯3) were divided into two groups by random. The patients received oral licorice or placebo syrups with a dose of 5â¯cc, twice a day for 6 months. High-performance liquid chromatography and spectrophotometric instruments determined licorice syrup constituents. The patients' situation for Unified Parkinson's rating scale (UPDRS) was assessed every 6 weeks for the duration of six months. In addition, patients' blood pressure, blood glucose, sodium and potassium levels, quality of life and dizziness were determined. RESULTS: Six weeks after intervention, total UPDRS, daily activities and tremor were significantly improved with a considerable effect size. A significant better motor test and rigidity scores were observed 4 months after licorice intake (pâ¯>â¯0.05). No electrolyte abnormality, significant changes in blood pressure or blood glucose levels were observed during the study. Each 5cc of syrup contained 136â¯mg of licorice extract with 12.14â¯mg glycyrrhizic acid, and also 136⯵g of polyphenols. CONCLUSION: The licorice intake could improve the symptoms in PD patients without serious adverse events.
Asunto(s)
Antiparkinsonianos/administración & dosificación , Glycyrrhiza/química , Enfermedad de Parkinson/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Antiparkinsonianos/efectos adversos , Glucemia/análisis , Glucemia/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Quimioterapia Combinada/métodos , Etnofarmacología , Femenino , Humanos , Irán , Masculino , Medicina Arábiga/métodos , Persona de Mediana Edad , Destreza Motora/efectos de los fármacos , Rigidez Muscular/sangre , Rigidez Muscular/tratamiento farmacológico , Rigidez Muscular/etiología , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/complicaciones , Placebos , Extractos Vegetales/efectos adversos , Raíces de Plantas/química , Calidad de Vida , Resultado del TratamientoRESUMEN
OBJECTIVE: To describe a novel and distinct variant of progressive encephalomyelitis with rigidity and myoclonus (PERM) associated with antibodies directed against dipeptidyl peptidase-like protein 6 (DPPX), a regulatory subunit of the Kv4.2 potassium channels on the surface of neurons. METHODS: Case series describing the clinical, paraclinical, and serologic features of 3 patients with PERM. A recombinant, cell-based indirect immunofluorescence assay with DPPX-expressing HEK293 cells was used to detect DPPX antibodies in conjunction with mammalian tissues. RESULTS: All patients presented with a distinct syndrome involving hyperekplexia, prominent cerebellar ataxia with marked eye movement disorder, and trunk stiffness of variable intensity. Additional symptoms comprised allodynia, neurogenic pruritus, and gastrointestinal symptoms. Symptoms began insidiously and progressed slowly. An inflammatory CSF profile with mild pleocytosis and intrathecal immunoglobulin G synthesis was found in all patients. High DPPX antibody titers were detected in the patients' serum and CSF, with specific antibody indices suggestive of intrathecal synthesis of DPPX antibodies. Response to immunotherapy was good, but constant and aggressive treatment may be required. CONCLUSION: These cases highlight the expanding spectrum of both PERM and anti-neuronal antibodies. Testing for DPPX antibodies should be considered in the diagnostic workup of patients with acquired hyperekplexia, cerebellar ataxia, and stiffness, because such patients might benefit from immunotherapy. Further studies are needed to elucidate both the entire clinical spectrum associated with DPPX antibodies and their role in pathogenesis.
Asunto(s)
Anticuerpos/sangre , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/inmunología , Encefalomielitis/sangre , Rigidez Muscular/sangre , Mioclonía/sangre , Proteínas del Tejido Nervioso/inmunología , Canales de Potasio/inmunología , Adolescente , Adulto , Anticuerpos/líquido cefalorraquídeo , Encéfalo/metabolismo , Encéfalo/patología , Electromiografía , Encefalomielitis/complicaciones , Encefalomielitis/tratamiento farmacológico , Encefalomielitis/inmunología , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Masculino , Rigidez Muscular/complicaciones , Rigidez Muscular/tratamiento farmacológico , Rigidez Muscular/inmunología , Mioclonía/complicaciones , Mioclonía/tratamiento farmacológico , Mioclonía/inmunología , Adulto JovenRESUMEN
Glycine receptor (GlyR) antibodies have been identified in patients with rigidity and hyperekplexia, but the clinical phenotype associated with these antibodies has not been fully elucidated. The clinical features in two additional patients with GlyR antibodies are described. A 55-year-old man presented with stimulus-induced hyperekplexia and rigidity in the lower limbs and trunk. He initially responded to benzodiazepines, but presented after 18 months with severe, painful, prolonged spasms associated with supraventricular and ventricular arrhythmias, hypoventilation and oxygen desaturation requiring intubation. He improved following treatment with clonazepam, baclofen and immunomodulatory therapies. A 58-year-old woman presented with stiffness in the legs and hyperekplexia associated with hypoventilation, at times leading to loss of consciousness. She responded to benzodiazepines and has remained in remission. The clinical picture associated with GlyR antibodies includes autonomic dysfunction, cardiac arrhythmias and hypoventilation. It is important to recognise these serious complications early to limit mortality from this treatable condition.
Asunto(s)
Autoanticuerpos , Encefalomielitis/diagnóstico , Hipoventilación/diagnóstico , Rigidez Muscular/diagnóstico , Mioclonía/diagnóstico , Receptores de Glicina , Autoanticuerpos/sangre , Encefalomielitis/sangre , Encefalomielitis/complicaciones , Femenino , Humanos , Hipoventilación/sangre , Hipoventilación/etiología , Masculino , Persona de Mediana Edad , Rigidez Muscular/sangre , Rigidez Muscular/complicaciones , Mioclonía/sangre , Mioclonía/complicaciones , Receptores de Glicina/sangreRESUMEN
IMPORTANCE: Progressive encephalomyelitis with rigidity and myoclonus is characterized by rigidity, painful muscle spasms, hyperekplexia, and brainstem signs. Recently, glycine receptor alpha 1 antibodies have been described in adult patients with progressive encephalomyelitis with rigidity and myoclonus. We describe a pediatric case. OBSERVATIONS: A 14-month-old child developed startle-induced episodes of generalized rigidity and myoclonus, axial hyperextension, and trismus, without impairment of consciousness. Episodes occurred during wakefulness and sleep, lasted seconds, and were accompanied by moaning, tachypnea, and oxygen desaturation. Imaging, cerebrospinal fluid, endocrine, metabolic, and genetic screening findings were normal or negative. She was treated with intravenous steroids and immunoglobulins with resolution of symptoms, but she relapsed weeks later. At this time, episodes were more severe. Glycine receptor alpha 1 antibodies were found in serum (titer of 1:200, later 1:320) and cerebrospinal fluid (titer of 1:2). Treatment was restarted with intravenous steroids and immunoglobulins, with major improvement, and she began treatment with oral steroids. She had 4 milder relapses, with improvement after treatment adjustments. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first pediatric case of progressive encephalomyelitis with rigidity and myoclonus associated with glycine receptor alpha 1 antibodies, a potentially severe but treatable antibody-mediated neurological disorder.
Asunto(s)
Mioclonía/complicaciones , Receptores de Glicina/inmunología , Encefalomielitis/sangre , Encefalomielitis/líquido cefalorraquídeo , Encefalomielitis/complicaciones , Encefalomielitis/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulinas/sangre , Inmunoglobulinas/líquido cefalorraquídeo , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Lactante , Rigidez Muscular/sangre , Rigidez Muscular/líquido cefalorraquídeo , Rigidez Muscular/complicaciones , Rigidez Muscular/tratamiento farmacológico , Mioclonía/sangre , Mioclonía/líquido cefalorraquídeo , Mioclonía/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Esteroides/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: To better characterize progressive encephalomyelitis with rigidity and myoclonus (PERM) syndrome and identify novel PERM phenotypes. METHODS: The clinical features and antibody status of PERM patients were investigated using immunoblots, cell-based assays, RIA, protein macroarray and ELISA. RESULTS: Two patients with supratentorial involvement showed abnormal PET or EEG findings. One patient was discovered to have renal cell carcinoma, and protein macroarray revealed Ma3-antibodies. Another patient with leucine-rich, glioma-inactivated 1 (LGI1) and glutamic acid decarboxylase (GAD) antibodies showed a good response to immunotherapy. CONCLUSION: The heterogeneity of the immunological features suggests that PERM is caused by diverse pathogenic mechanisms. Seropositivity to well-characterized neuronal cell surface antigens might indicate a good treatment response.
Asunto(s)
Autoanticuerpos/sangre , Encefalomielitis/sangre , Encefalomielitis/complicaciones , Rigidez Muscular/sangre , Rigidez Muscular/complicaciones , Mioclonía/sangre , Mioclonía/complicaciones , Anciano , Encefalomielitis/tratamiento farmacológico , Ensayo de Inmunoadsorción Enzimática , Glutamato Descarboxilasa/inmunología , Células HEK293 , Humanos , Inmunosupresores/uso terapéutico , Péptidos y Proteínas de Señalización Intracelular , Canales Iónicos/inmunología , Masculino , Proteínas de la Membrana/inmunología , Persona de Mediana Edad , Rigidez Muscular/tratamiento farmacológico , Mioclonía/terapia , Proteínas del Tejido Nervioso/inmunología , Análisis por Matrices de Proteínas , Proteínas/inmunología , TransfecciónAsunto(s)
Anticuerpos/sangre , Anticuerpos/líquido cefalorraquídeo , Encefalomielitis/sangre , Encefalomielitis/líquido cefalorraquídeo , Metilprednisolona/uso terapéutico , Rigidez Muscular/sangre , Rigidez Muscular/líquido cefalorraquídeo , Mioclonía/inmunología , Receptores de Glicina/metabolismo , Adulto , Encefalomielitis/tratamiento farmacológico , Encefalomielitis/fisiopatología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Rigidez Muscular/tratamiento farmacológico , Rigidez Muscular/fisiopatología , Mioclonía/complicaciones , Receptores de Glicina/inmunologíaRESUMEN
BACKGROUND: The syndrome of progressive encephalopathy with limb rigidity has been historically termed progressive encephalomyelitis with rigidity and myoclonus (PERM) or stiff-person syndrome plus. METHODS: The case is presented of a previously healthy 28-year-old man with a rapidly fatal form of PERM developing over 2 months. RESULTS: Serum antibodies to both NMDA receptors (NMDAR) and glycine receptors (GlyR) were detected postmortem, and examination of the brain confirmed an autoimmune encephalomyelitis, with particular involvement of hippocampal pyramidal and cerebellar Purkinje cells and relative sparing of the neocortex. No evidence for an underlying systemic neoplasm was found. CONCLUSION: This case displayed not only the clinical features of PERM, previously associated with GlyR antibodies, but also some of the features associated with NMDAR antibodies. This unusual combination of antibodies may be responsible for the particularly progressive course and sudden death.
Asunto(s)
Anticuerpos/sangre , Encefalomielitis/sangre , Rigidez Muscular/sangre , Mioclonía/sangre , Receptores de Glicina/inmunología , Receptores de N-Metil-D-Aspartato/inmunología , Adulto , Encéfalo/patología , Encefalomielitis/complicaciones , Encefalomielitis/patología , Humanos , Masculino , Rigidez Muscular/complicaciones , Rigidez Muscular/patología , Mioclonía/complicaciones , Mioclonía/patología , Médula Espinal/patologíaRESUMEN
The effect on increased myotatic reflexes of desmethyldiazepam, formed from its precursor clorazepate, was assessed in a double-blind cross-over study of 27 days duration. Eight patients with spasticity or rigidity were given placebo or active substance; first in loading doses for 2 days, then 5 mg every 12 h for a total of 10 days. A wash-out period of 7 days was interposed between the 2 10-day periods. Desmethyldiazepam had a normalizing effect on the increased phasic ankle reflexes seen in spasticity, but not on the increased tonic reflex seen in rigidity. The mean concentration of desmethyldiazepam in the steady state was 1227 nmol/l (range 600-1990 nmol/l). The plasma concentration of desmethyldiazepam tended to correlate with the percent decrease in phasic reflex activity (P = 0.08, 2-tailed). A slight drowsiness in 2 patients was the only side-effect seen. In conclusion, desmethyldiazepam given as clorazepate seems to be a suitable medicament in the treatment of spasticity.