RARE DISEASE
Postencephalitic parkinsonism
Postencephalitic parkinsonism
Postencephalitic parkinsonism
Drug discovery
0
drugs
With orphan designations
Overview
Postencephalitic parkinsonism (PEP) is a secondary parkinsonian syndrome triggered by viral encephalitis, historically linked to encephalitis lethargica (1917–1928). It manifests with bradykinesia, rigidity, oculogyric crises, and postural instability, often delayed by years after acute infection. Neuropathology shows tau-based neurofibrillary tangles in the substantia nigra without Lewy bodies or iron deposition [1][4][7]. Unlike idiopathic Parkinson’s disease, PEP has limited response to levodopa and higher susceptibility to psychiatric complications [3][8]. Diagnosis relies on clinical history and exclusion of other causes [6].
Therapies
Levodopa: Modest, transient motor improvement but induces dyskinesias/psychosis at low doses [3][8].
Supportive care: Physiotherapy, speech therapy, and ECT for severe psychiatric symptoms [2][18].
No disease-modifying treatments: Focus on symptom management with corticosteroids for acute inflammation [2][4].
Categories: rare neurological diseases
Research Papers
87 drug discovery papers about Postencephalitic parkinsonism, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
87 drug discovery papers about Postencephalitic parkinsonism, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-02-17 | Chikungunya-associated encephalitis with postencephalitic parkinsonism in an elderly woman: a case report
Chikungunya virus infection usually manifests with fever, rash, and arthralgia, but neurological involvement is rare and post-encephalitic parkinsonism is exceptionally uncommon. We report a 70-year-old diabetic, hypertensive woman who developed altered consciousness after febrile illness and polyarthritis during a chikungunya outbreak. Magnetic Resonance Imaging of brain revealed bilateral basal ganglia hyperintensities with diffusion restriction, and cerebrospinal fluid analysis showed lymphocytic pleocytosis, elevated protein, and chikungunya viral polymerase chain reaction positivity. She improved with intravenous immunoglobulin, but subsequently developed parkinsonian features one month later, consistent with post-encephalitic Parkinsonism, which responded to Dopaminergic therapy. This case highlights that chikungunya virus can rarely cause central nervous system involvement with delayed parkinsonism, underscoring the need for early recognition, immunotherapy, and long-term neurological follow-up. BIRDEM Med J 2026; 16(1): 36-39
2024-12-23 | Crexont — Extended-Release Carbidopa/Levodopa for Parkinson's Disease
The FDA has approved Crexont (Amneal), an extended-release capsule formulation of carbidopa/levodopa, for treatment of Parkinson's disease (PD), postencephalitic parkinsonism, and parkinsonism associated with carbon monoxide or manganese intoxication. Crexont contains a combination of immediate-release carbidopa/levodopa granules and extended-release levodopa pellets. An extended-release carbidopa/levodopa oral capsule (Rytary) has been available from the same manufacturer for years; the patent for Rytary expires in 2025.
2024-03-22 | Herbis, non verbis, fiunt medicamenta vitae: The Italian botanist Arturo Nannizzi (1887-1961) and his contribution to the treatment of parkinsonism following encephalitis lethargica.
We describe the Italian contribution to the description and treatment of parkinsonism following encephalitis lethargica (EL): postencephalitic parkinsonism (PEP). Special attention is devoted to the description of postencephalitic symptoms by Giuseppe Panegrossi (1871-1953) and to the treatment based on Atropa belladonna introduced in Italy and extensively supported by Arturo Nannizzi (1887-1961), who was charged by the queen of Italy with conducting research into this plant and advocating its cultivation for healing purposes. This article gives us the unique opportunity to revisit the figure of this distinguished botanist, providing a summary of his biography, interests, and achievements.
2023-06-19 | A Half-century of Awakenings
Fifty years have passed since the 1973 publication of Awakenings , a remarkable book by a remarkable author, Oliver Sacks.1 At the time he wrote it, Sacks was a newly minted neurologist and, approaching age 40 years, struggling to find his place in the world. By chance, he sought work at a hospital in New York that housed patients who, decades earlier, contracted encephalitis lethargica. First encountered in Vienna in 1916, the epidemic of this mysterious malady (also known as von Economo disease) spread worldwide over the following decade, killing thousands young and old. Survivors developed lasting neurologic impairments including Parkinsonism and catatonic states.2,3 For decades afterward, hundreds of victims remained in chronic care wards. As recounted in Awakenings and in a later autobiographical memoir,4 Sacks was fascinated by the aftermath of this disorder. He was equally intrigued as to how his patients might respond to levodopa, a novel treatment recently developed for Parkinson disease. Previously, a few English postencephalitic patients had shown improvements with levodopa.5 Sacks initiated a small placebo-controlled trial and, after encountering promising results, began to treat other postencephalitic survivors. Although the extraordinary pharmacologic outcomes he encountered might have been sufficient material for a good tale, Sacks envisioned a far more encompassing project for his book.
2021-12-20 | Astrocyte inflammatory signaling mediates α-synuclein aggregation and dopaminergic neuronal loss following viral encephalitis.
Viral infection of the central nervous system (CNS) can cause lasting neurological decline in surviving patients and can present with symptoms resembling Parkinson's disease (PD). The mechanisms underlying postencephalitic parkinsonism remain unclear but are thought to involve increased innate inflammatory signaling in glial cells, resulting in persistent neuroinflammation. We therefore studied the role of glial cells in regulating neuropathology in postencephalitic parkinsonism by studying the involvement of astrocytes in loss of dopaminergic neurons and aggregation of α-synuclein protein following infection with western equine encephalitis virus (WEEV). Infections were conducted in both wildtype mice and in transgenic mice lacking NFκB inflammatory signaling in astrocytes. For 2 months following WEEV infection, we analyzed glial activation, neuronal loss and protein aggregation across multiple brain regions, including the substantia nigra pars compacta (SNpc). These data revealed that WEEV induces loss of SNpc dopaminergic neurons, persistent activation of microglia and astrocytes that precipitates widespread aggregation of α-synuclein in the brain of C57BL/6 mice. Microgliosis and macrophage infiltration occurred prior to activation of astrocytes and was followed by opsonization of ⍺-synuclein protein aggregates in the cortex, hippocampus and midbrain by the complement protein, C3. Astrocyte-specific NFκB knockout mice had reduced gliosis, α-synuclein aggregate formation and neuronal loss. These data suggest that astrocytes play a critical role in initiating PD-like pathology following encephalitic infection with WEEV through innate immune inflammatory pathways that damage dopaminergic neurons, possibly by hindering clearance of ⍺-synuclein aggregates. Inhibiting glial inflammatory responses could therefore represent a potential therapy strategy for viral parkinsonism.
antibodies
2024-07-13 | Prolactin: A Mammalian Stress Hormone and Its Role in Cutaneous Pathophysiology.
The hormone prolactin (PRL) is best recognised for its indispensable role in mammalian biology, specifically the regulation of lactation. Bearing in mind that the mammary gland is a modified sweat gland, it is perhaps unsurprising to discover that PRL also plays a significant role in cutaneous biology and is implicated in the pathogenesis of a range of skin diseases, often those reportedly triggered and/or exacerbated by psychological stress. Given that PRL has been implicated in over 300 biological processes, spanning reproduction and hair growth and thermo- to immunoregulation, a comprehensive understanding of the relationship between PRL and the skin remains frustratingly elusive. In an historical curiosity, the first hint that PRL could affect skin biology came from the observation of seborrhoea in patients with post-encephalitic Parkinsonism as a result of another global pandemic, encephalitis lethargica, at the beginning of the last century. As PRL is now being postulated as a potential immunomodulator for COVID-19 infection, it is perhaps timeous to re-examine this pluripotent hormone with cytokine-like properties in the cutaneous context, drawing together our understanding of the role of PRL in skin disease to illustrate how targeting PRL-mediated signalling may represent a novel strategy to treat a range of skin diseases and hair disorders.
2016-04-27 | Post-Encephalitic Parkinsonism and Sleep Disorder Responsive to Immunological Treatment
We describe a 70-year-old man who, after a viral encephalitis associated with pneumonia, progressively developed a parkinsonism associated with lethargy. Encephalitis manifested with persistent hiccups, seizures and impairment of consciousness. After 2 weeks, the initial neurologic symptoms subsided and the patient progressively developed movement disorders (rigidity and bradykinesia, resistant to L-DOPA), lethargy and behavioral hypersomnia. Magnetic resonance imaging showed thalamic and hippocampal signal abnormalities, immunohistochemistry on a mouse brain substrate revealed serum autoantibodies binding to the brainstem neuropil. Polysomnographic monitoring was consistent with a very severe disruption of sleep: the sleep-wake cycle was fragmented, and the NREM-REM ultradian cycle was irregular. Intravenous immune globulin therapy resulted in the complete reversal of the movement and the sleep disorders. Our observation confirms that parkinsonism and sleep disorders may be consequences of encephalitis, that an immune-mediated pathogenesis is likely, and, consequently, that immunotherapy can be beneficial in these patients. The polysomnographic monitoring suggests that lethargia, rather than a mere hypersomnia, is the result of a combination between sleep disruption and altered motor control.
2009-08-10 | Contemporary Encephalitis Lethargica: phenotype, laboratory findings and treatment outcomes.
Encephalitis lethargica (EL) is a CNS disorder that manifests with lethargy sleep cycle disturbances, extrapyramidal symptomatology, neuropsychiatric manifestations, ocular features and cardio-respiratory abnormalities. Although there have been no reported outbreaks of EL recently, a number of reports show that cases of EL are still encountered regularly. Against this background we conducted a study aiming to elucidate the clinical characteristics, describe laboratory/ neuroimaging findings (MRI, PET) and present treatment options and outcomes in sporadic EL. Patients were diagnosed over a period of 3 years using proposed diagnostic criteria. Extensive laboratory and imaging tests were performed for exclusion of other causes. Anti-neuronal antibodies against human basal ganglia were detected with western immunoblotting and (18)F-FDG PET imaging was performed. Selected cases were videotaped. Our patients (M/F: 5/3) ranged from 2-28 years (mean 9.3 +/- 9.5). Encephalopathy, sleep disturbances and extrapyramidal symptoms were present in all cases. Laboratory investigations revealed CSF leukocytosis in 5/8 patients and anti-BG Ab in 4/7 patients. MRIs revealed structural abnormalities in 7/8 cases. (18)F-FDG PET showed basal ganglionic hypermetabolism in 4/7 patients. Treatment approaches included immunomodulating and symptomatic therapies. We report no mortality from EL in our series. There seems to be little doubt that cases of EL still occur. Diagnosis may be based on clinical suspicion and laboratory/imaging tests may lead to early initiation of immunomodulating and supporting therapies. We suggest that in addition to anti-BG Abs FDG PET should be considered as a diagnostic tool for EL.
small molecules
2026-02-17 | Chikungunya-associated encephalitis with postencephalitic parkinsonism in an elderly woman: a case report
Chikungunya virus infection usually manifests with fever, rash, and arthralgia, but neurological involvement is rare and post-encephalitic parkinsonism is exceptionally uncommon. We report a 70-year-old diabetic, hypertensive woman who developed altered consciousness after febrile illness and polyarthritis during a chikungunya outbreak. Magnetic Resonance Imaging of brain revealed bilateral basal ganglia hyperintensities with diffusion restriction, and cerebrospinal fluid analysis showed lymphocytic pleocytosis, elevated protein, and chikungunya viral polymerase chain reaction positivity. She improved with intravenous immunoglobulin, but subsequently developed parkinsonian features one month later, consistent with post-encephalitic Parkinsonism, which responded to Dopaminergic therapy. This case highlights that chikungunya virus can rarely cause central nervous system involvement with delayed parkinsonism, underscoring the need for early recognition, immunotherapy, and long-term neurological follow-up. BIRDEM Med J 2026; 16(1): 36-39
2024-12-23 | Crexont — Extended-Release Carbidopa/Levodopa for Parkinson's Disease
The FDA has approved Crexont (Amneal), an extended-release capsule formulation of carbidopa/levodopa, for treatment of Parkinson's disease (PD), postencephalitic parkinsonism, and parkinsonism associated with carbon monoxide or manganese intoxication. Crexont contains a combination of immediate-release carbidopa/levodopa granules and extended-release levodopa pellets. An extended-release carbidopa/levodopa oral capsule (Rytary) has been available from the same manufacturer for years; the patent for Rytary expires in 2025.
2024-03-22 | Herbis, non verbis, fiunt medicamenta vitae: The Italian botanist Arturo Nannizzi (1887-1961) and his contribution to the treatment of parkinsonism following encephalitis lethargica.
We describe the Italian contribution to the description and treatment of parkinsonism following encephalitis lethargica (EL): postencephalitic parkinsonism (PEP). Special attention is devoted to the description of postencephalitic symptoms by Giuseppe Panegrossi (1871-1953) and to the treatment based on Atropa belladonna introduced in Italy and extensively supported by Arturo Nannizzi (1887-1961), who was charged by the queen of Italy with conducting research into this plant and advocating its cultivation for healing purposes. This article gives us the unique opportunity to revisit the figure of this distinguished botanist, providing a summary of his biography, interests, and achievements.
2023-06-19 | A Half-century of Awakenings
Fifty years have passed since the 1973 publication of Awakenings , a remarkable book by a remarkable author, Oliver Sacks.1 At the time he wrote it, Sacks was a newly minted neurologist and, approaching age 40 years, struggling to find his place in the world. By chance, he sought work at a hospital in New York that housed patients who, decades earlier, contracted encephalitis lethargica. First encountered in Vienna in 1916, the epidemic of this mysterious malady (also known as von Economo disease) spread worldwide over the following decade, killing thousands young and old. Survivors developed lasting neurologic impairments including Parkinsonism and catatonic states.2,3 For decades afterward, hundreds of victims remained in chronic care wards. As recounted in Awakenings and in a later autobiographical memoir,4 Sacks was fascinated by the aftermath of this disorder. He was equally intrigued as to how his patients might respond to levodopa, a novel treatment recently developed for Parkinson disease. Previously, a few English postencephalitic patients had shown improvements with levodopa.5 Sacks initiated a small placebo-controlled trial and, after encountering promising results, began to treat other postencephalitic survivors. Although the extraordinary pharmacologic outcomes he encountered might have been sufficient material for a good tale, Sacks envisioned a far more encompassing project for his book.
2021-12-20 | Astrocyte inflammatory signaling mediates α-synuclein aggregation and dopaminergic neuronal loss following viral encephalitis.
Viral infection of the central nervous system (CNS) can cause lasting neurological decline in surviving patients and can present with symptoms resembling Parkinson's disease (PD). The mechanisms underlying postencephalitic parkinsonism remain unclear but are thought to involve increased innate inflammatory signaling in glial cells, resulting in persistent neuroinflammation. We therefore studied the role of glial cells in regulating neuropathology in postencephalitic parkinsonism by studying the involvement of astrocytes in loss of dopaminergic neurons and aggregation of α-synuclein protein following infection with western equine encephalitis virus (WEEV). Infections were conducted in both wildtype mice and in transgenic mice lacking NFκB inflammatory signaling in astrocytes. For 2 months following WEEV infection, we analyzed glial activation, neuronal loss and protein aggregation across multiple brain regions, including the substantia nigra pars compacta (SNpc). These data revealed that WEEV induces loss of SNpc dopaminergic neurons, persistent activation of microglia and astrocytes that precipitates widespread aggregation of α-synuclein in the brain of C57BL/6 mice. Microgliosis and macrophage infiltration occurred prior to activation of astrocytes and was followed by opsonization of ⍺-synuclein protein aggregates in the cortex, hippocampus and midbrain by the complement protein, C3. Astrocyte-specific NFκB knockout mice had reduced gliosis, α-synuclein aggregate formation and neuronal loss. These data suggest that astrocytes play a critical role in initiating PD-like pathology following encephalitic infection with WEEV through innate immune inflammatory pathways that damage dopaminergic neurons, possibly by hindering clearance of ⍺-synuclein aggregates. Inhibiting glial inflammatory responses could therefore represent a potential therapy strategy for viral parkinsonism.
antibodies
2024-07-13 | Prolactin: A Mammalian Stress Hormone and Its Role in Cutaneous Pathophysiology.
The hormone prolactin (PRL) is best recognised for its indispensable role in mammalian biology, specifically the regulation of lactation. Bearing in mind that the mammary gland is a modified sweat gland, it is perhaps unsurprising to discover that PRL also plays a significant role in cutaneous biology and is implicated in the pathogenesis of a range of skin diseases, often those reportedly triggered and/or exacerbated by psychological stress. Given that PRL has been implicated in over 300 biological processes, spanning reproduction and hair growth and thermo- to immunoregulation, a comprehensive understanding of the relationship between PRL and the skin remains frustratingly elusive. In an historical curiosity, the first hint that PRL could affect skin biology came from the observation of seborrhoea in patients with post-encephalitic Parkinsonism as a result of another global pandemic, encephalitis lethargica, at the beginning of the last century. As PRL is now being postulated as a potential immunomodulator for COVID-19 infection, it is perhaps timeous to re-examine this pluripotent hormone with cytokine-like properties in the cutaneous context, drawing together our understanding of the role of PRL in skin disease to illustrate how targeting PRL-mediated signalling may represent a novel strategy to treat a range of skin diseases and hair disorders.
2016-04-27 | Post-Encephalitic Parkinsonism and Sleep Disorder Responsive to Immunological Treatment
We describe a 70-year-old man who, after a viral encephalitis associated with pneumonia, progressively developed a parkinsonism associated with lethargy. Encephalitis manifested with persistent hiccups, seizures and impairment of consciousness. After 2 weeks, the initial neurologic symptoms subsided and the patient progressively developed movement disorders (rigidity and bradykinesia, resistant to L-DOPA), lethargy and behavioral hypersomnia. Magnetic resonance imaging showed thalamic and hippocampal signal abnormalities, immunohistochemistry on a mouse brain substrate revealed serum autoantibodies binding to the brainstem neuropil. Polysomnographic monitoring was consistent with a very severe disruption of sleep: the sleep-wake cycle was fragmented, and the NREM-REM ultradian cycle was irregular. Intravenous immune globulin therapy resulted in the complete reversal of the movement and the sleep disorders. Our observation confirms that parkinsonism and sleep disorders may be consequences of encephalitis, that an immune-mediated pathogenesis is likely, and, consequently, that immunotherapy can be beneficial in these patients. The polysomnographic monitoring suggests that lethargia, rather than a mere hypersomnia, is the result of a combination between sleep disruption and altered motor control.
2009-08-10 | Contemporary Encephalitis Lethargica: phenotype, laboratory findings and treatment outcomes.
Encephalitis lethargica (EL) is a CNS disorder that manifests with lethargy sleep cycle disturbances, extrapyramidal symptomatology, neuropsychiatric manifestations, ocular features and cardio-respiratory abnormalities. Although there have been no reported outbreaks of EL recently, a number of reports show that cases of EL are still encountered regularly. Against this background we conducted a study aiming to elucidate the clinical characteristics, describe laboratory/ neuroimaging findings (MRI, PET) and present treatment options and outcomes in sporadic EL. Patients were diagnosed over a period of 3 years using proposed diagnostic criteria. Extensive laboratory and imaging tests were performed for exclusion of other causes. Anti-neuronal antibodies against human basal ganglia were detected with western immunoblotting and (18)F-FDG PET imaging was performed. Selected cases were videotaped. Our patients (M/F: 5/3) ranged from 2-28 years (mean 9.3 +/- 9.5). Encephalopathy, sleep disturbances and extrapyramidal symptoms were present in all cases. Laboratory investigations revealed CSF leukocytosis in 5/8 patients and anti-BG Ab in 4/7 patients. MRIs revealed structural abnormalities in 7/8 cases. (18)F-FDG PET showed basal ganglionic hypermetabolism in 4/7 patients. Treatment approaches included immunomodulating and symptomatic therapies. We report no mortality from EL in our series. There seems to be little doubt that cases of EL still occur. Diagnosis may be based on clinical suspicion and laboratory/imaging tests may lead to early initiation of immunomodulating and supporting therapies. We suggest that in addition to anti-BG Abs FDG PET should be considered as a diagnostic tool for EL.
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