After the recent description of biphasic disease with herpes simplex virus (HSV) encephalitis
followed by anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE), anti-NMDARE
preceded by non-HSV central nervous system (CNS) infection has been more rarely reported.
(The Lancet Psychiatry) – N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis is a neuropsychiatric disorder1, 2 that is caused by antibodies against the NR1 subunit of the NMDA receptor. Many patients with NMDAR-antibody encephalitis are…
A fifth case of limbic encephalitis associated with GAD antibodies and HHV-6 infection has been reported, this time in an immunocompetent woman with chromosomally integrated HHV-6, epilepsy, and psychosis. The patient’s condition improved (with a drop in GAD antibody titers and stabilization of psychotic symptoms) in response to three weeks of antiviral therapy but relapsed when antiviral therapy was withdrawn. Previously, the same neuropathology group in Germany reported two GAD-antibody-positive limbic encephalitis patients with HHV-6 DNA detected in surgically removed hippocampal tissue (Niehusmann 2010). Another publication reported two patients who had HHV-6-associated limbic encephalitis, autoimmune thyroid disease, and elevated antibodies to GAD (Mata 2008). GAD antibodies occur in a number of neurological disorders, and when the antibodies are extremely high, they can cause Stiff Person Syndrome. High level GAD antibodies define a relevant group of patients with chronic, nonremitting, and nonparaneoplastic limbic encephalitis (Malter 2010). At low levels, these antibodies are a predictive factor for type 1 diabetes. The authors note that antibodies against NMDAR, the surface protein N-methyl-D-aspartate receptor, have been identified as a cause of encephalopathy post HSV-1 encephalitis, and speculate that HHV-6 may trigger a similar cascade. They recommend further study to determine the frequency of simultaneous active HHV-6 infection and GAD65 antibodies. Of interest, a 1998 report identified GAD65 antibody stimulation in response to the HHV-6 U2 gene, via mimicry (Bach 1998). HHV-6 reactivation has been linked to many of the conditions associated with GAD antibodies. For example, HHV-6 reactivation has been found in cases of fulminant type 1 diabetes after drug induced hypersensitivity syndrome (DIHS). In one series, HHV-6 reactivation was linked to 11 cases of fulminant type 1 diabetes (Onuma 2012). Two other cases of drug hypersensitivity and type 1 diabetes were reported by Taiwanese investigators in association with DRESS (Chiou 2006). Immunohistochemistry of brain tissue from this case showed T-lymphocytic infiltrates, a moderate activation of microglia, and moderate reactive astrogliosis. Anti-neuronal antibodies binding to pyramidal cells of the hippocampus and cerebellar Purkinje cells within the serum and CSF were identified using an indirect immunohistochemistry approach. The study was led by neuropathologist Pitt Niehusmann, MD from University Hospital Oslo, Norway and Albert Becker, MD from the Translational Epilepsy Research Section at the University of Bonn, Germany. For more information, read the full paper (Niehusmann 2016).
Twelve months ago, young Perth woman Ariana Pila spent most of her days in a comatose state, unable to eat, walk or talk. Today, the 21-year-old is making plans to walk the Great Wall of China, as well as study and work, thanks to an astonishing recovery from a rare autoimmune disease. She has got rid of her wheelchair, feeding tube and tracheostomy tube. With the help of therapists and her stubbornly determined personality, she has learned to sit, stand, walk and climb the stairs to her bedroom at home — and now she wants to take up jogging. “She always says ‘I can’t do it’, but once she makes that first step past that word ‘can’t’ and that fear, then all confidence comes in and she just smashes it,” her mother, Kirstine Bruce, said. Struck down in her teens Five years ago, a 16-year-old Ms Pila collapsed in a fast food restaurant with anti-NMDA receptor encephalitis, a disease causing brain inflammation and psychiatric symptoms. Doctors held little hope she would ever regain any of her cognitive or physical abilities. “She was in a severely vegetative state,” Ms Bruce said. “Thrashing. Her body was thrashing about the bed for the majority of the time. “High temps, high blood pressure, just absolutely everything.” After being discharged from hospital, Ms Pila was forced to live in an aged care facility where she had little physiotherapy and spent her days watching television. Her mother saw occasional signs of a spark in her daughter and agitated for a different course of treatment for her, but it was a struggle. “We couldn’t get any help for her,” she said. “Because she was so severely vegetative, everyone was fobbing her off, saying, ‘No, there’s nothing we can do, she’s got to fit a certain criteria’. “Everyone wrote her off.” Now, after five months of intensive therapy at Perth disability services organisation Rocky Bay, as well as Fiona Stanley Hospital, Ms Pila has broken down physical barrier after physical barrier. “They doubted me that I was going to walk,” she said. “They even thought that I wasn’t ever going to wake up.” Rare disease began with headaches Anti-NMDA receptor encephalitis was only identified as a condition in 2007, and it is understood only a few thousand people have been diagnosed with it worldwide. It affects the receptors in the brain which control, among other things, memory function. In Ms Pila’s case, the disease has been linked to a benign teratoma tumour on her left ovary. Ms Bruce said her daughter was lucky to be diagnosed by her neurologist because many in her situation were incorrectly treated for mental health disorders like schizophrenia. Some neurologists believed many more people could have the disease but had been misdiagnosed. For Ms Pila, the onset of her disease began with headaches at age 13. She began to act strangely — “like bipolar, schizophrenic behaviours,” Ms Bruce said — and then suffered memory loss. In April 2013, she deteriorated rapidly. After collapsing in the fast-food restaurant, she was taken to hospital and lost her ability to talk three days later. Five lost years Five years to the day later, Ms Pila began to speak again. Her first words were, “Hey Mama”. But there were reminders of Ms Pila’s lost teenage years, like the hole in her throat where her tracheostomy tube was inserted and the big chunks of her life missing from her memory. When she first began to wake from her comatose state about a year ago, she thought it was still 2012 and was shocked that her siblings looked so different. “She remembers everything from birth to 15 and then nothing from 16 to 21,” Ms Bruce said. “She missed her formative years.” But Ms Pila has big plans to fill in the gaps, starting with her first music concert next month. “She wants to work, she wants to study, she wants to go back home to New Zealand and we’re going to do the Great Wall of China in 2020, that’s what we’re working towards,” Ms Bruce said Ms Pila said she was proud of what she had achieved with the support of her family and therapy team. Her physiotherapist Jocelyn MacRae said the biggest factors behind Ms Pila’s recovery were her family support and sheer determination. “As much as she says ‘I can’t’ sometimes, she just breaks that barrier down and still gives it a go,” she said. “There’s never been a gym session where she hasn’t given it a go or worked hard at it.”
Case Reports in Neurological Medicine is a peer-reviewed, Open Access journal that publishes case reports and case series focusing on diseases of the nervous system, as well as abnormal neurological function.
Significant immunological alterations have been observed in women with first-onset affective psychosis during the postpartum period. Recent studies have highlighted the possibility that a subset of patients with first-onset severe psychiatric episodes …