Sex: F
Vaccine: FLUX, FLUX
Symptoms: Anti-neuronal antibody, Anti-neuronal antibody negative, Anti-thyroid antibody positive, Antiacetylcholine receptor antibody, Antinuclear antibody negative
Clinical narrative: insomnia; cognitive decline; language decline; catatonia; seizure; Autism spectrum disorder; Down syndrome disintegrative disorder; condition aggravated; acute onset insomnia; autistic characteristics/Autism spectrum disorder; catatonic symptoms; stupor; staring; posturing; stereotypy/mannerisms; verbigeration; rigidity; perseveration; mutism; echolalia; combativeness; cognitive decline; hallucinations; intelligence quotient (IQ) was decreased from 70 to 32; She became unable to read and perform activities of daily living; incontinent of urine; incontinent of stool; psychosis; seizures; catatonia did not respond to lorazepam; This case was reported in a literature article and described the occurrence of down's syndrome in a 17-year-old female subject who received Flu vaccine for prophylaxis.   Co-suspect products included Flu unspecified (Influenza vaccine) for prophylaxis and lorazepam unknown for catatonic.   The subject's past medical history included autoimmune disorder. Concurrent medical conditions included graves' disease (At the age of 7-years, with positive-titer thyroperoxidase antibodies), intellectual disability and down's syndrome (The onset of symptoms was after the age of 10 years and was treated with immunotherapy).   On an unknown date, 14 days after receiving Flu vaccine, the subject developed down's syndrome. Serious criteria included hospitalization. Additional event(s) included condition aggravated with serious criteria of hospitalization, insomnia with serious criteria of hospitalization, autistic behavior with serious criteria of hospitalization and GSK medically significant, severe - grade 3 catatonic with serious criteria of hospitalization, severe - grade 3 stupor with serious criteria of hospitalization, severe - grade 3 staring with serious criteria of hospitalization, severe - grade 3 posturing with serious criteria of hospitalization, severe - grade 3 stereotypy with serious criteria of hospitalization, severe - grade 3 verbigeration with serious criteria of hospitalization, severe - grade 3 rigidity with serious criteria of hospitalization, severe - grade 3 perseveration with serious criteria of hospitalization, mild - grade 1 mutism with serious criteria of hospitalization, mild - grade 1 echolalia with serious criteria of hospitalization, mild - grade 1 combative reaction with serious criteria of hospitalization, cognitive deterioration with serious criteria of hospitalization, hallucination with serious criteria of hospitalization, intelligence decreased with serious criteria of hospitalization and GSK medically significant, activities of daily living impaired with serious criteria of hospitalization, urinary incontinence with serious criteria of hospitalization, fecal incontinence with serious criteria of hospitalization, psychosis with serious criteria of hospitalization, seizure with serious criteria of hospitalization and GSK medically significant, severe - grade 3 insomnia with serious criteria of hospitalization, severe - grade 3 cognitive deterioration with serious criteria of hospitalization, severe - grade 3 language disorder with serious criteria of hospitalization, severe - grade 3 catatonic with serious criteria of hospitalization, severe - grade 3 seizure with serious criteria of hospitalization and GSK medically significant, autism spectrum disorder with serious criteria of hospitalization and GSK medically significant and lack of drug effect. The subject was treated with haloperidol, fluoxetine, lurasidone, methylprednisolone, immunoglobulins nos (Immunoglobulin) and mycophenolic acid (Mycophenolate). The outcome of down's syndrome was recovered/resolved. The outcome(s) of the additional event(s) included condition aggravated (recovered/resolved), insomnia (recovered/resolved), autistic behavior (recovered/resolved), catatonic (recovered/resolved), stupor (recovered/resolved), staring (recovered/resolved), posturing (recovered/resolved), stereotypy (recovered/resolved), verbigeration (recovered/resolved), rigidity (recovered/resolved), perseveration (recovered/resolved), mutism (recovered/resolved), echolalia (recovered/resolved), combative reaction (recovered/resolved), cognitive deterioration (recovered/resolved), hallucination (recovered/resolved), intelligence decreased (recovered/resolved), activities of daily living impaired (recovered/resolved), urinary incontinence (recovered/resolved), fecal incontinence (recovered/resolved), psychosis (recovered/resolved), seizure (recovered/resolved), insomnia (recovered/resolved), cognitive deterioration (recovered/resolved), language disorder (recovered/resolved), catatonic (recovered/resolved), seizure (recovered/resolved), autism spectrum disorder (recovered/resolved) and lack of drug effect (unknown).   The investigator considered that there was a reasonable possibility that the down's syndrome, condition aggravated, insomnia, autistic behavior, catatonic, stupor, staring, posturing, stereotypy, verbigeration, rigidity, perseveration, mutism, echolalia, combative reaction, cognitive deterioration, hallucination, intelligence decreased, activities of daily living impaired, urinary incontinence, fecal incontinence, psychosis and seizure may have been caused by Flu vaccine. It was unknown if the investigator considered the lack of drug effect to be related to Flu vaccine. Other possible cause(s) of the insomnia included INFLUENZA VIRUS VACCINE POLYVALENT. Other possible cause(s) of the cognitive deterioration included INFLUENZA VIRUS VACCINE POLYVALENT. Other possible cause(s) of the language disorder included INFLUENZA VIRUS VACCINE POLYVALENT. Other possible cause(s) of the catatonic included INFLUENZA VIRUS VACCINE POLYVALENT. Other possible cause(s) of the seizure included INFLUENZA VIRUS VACCINE POLYVALENT. Other possible cause(s) of the autism spectrum disorder included INFLUENZA VIRUS VACCINE POLYVALENT. Other possible cause(s) of the lack of drug effect included INFLUENZA VIRUS VACCINE POLYVALENT.   Relevant Tests: Lab tests were performed on unspecified dates. The patient's BFCRS (Bush-Francis Catatonia Rating Scale) out of 54 at baseline was 1, at pretreatment was 30. The AIS (Athens Insomnia Scale) out of 24, at baseline was 0, at pretreatment was 20. The ASD (Autism spectrum disorder) severity at baseline was none, at pretreatment was moderate. The oligoclonal bands and autoimmune encephalitis (AE) panel (CSF AE panel included N-methyl-D-aspartate, glutamic acid decarboxylase 65, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, gamma-aminobutyric acid receptor B subunit, collapsin response-mediator protein-5, amphiphysin, leucine-rich, glioma-inactivated 1, contactin-associated protein 2, voltage-gated potassium channel, antineuronal nuclear antibody 1, antineuronal nuclear antibody 2, antineuronal nuclear antibody 3, antiglial nuclear antibody, purkinje cell cytoplasmic antibody 1, 2, and Tr) was negative. The serum thyroid antibody showed microsomal positive. The autoimmune encephalitis (AE) panel (serum AE panel included above plus striational, N-type calcium channel, P/Q type calcium channel, and acetylcholine receptor) was negative. The patient had documented auto-antibodies. The patient's BFCRS post treatment was 0. The AIS (Athens Insomnia Scale) out of 24, at post treatment was 1. The ASD (Autism spectrum disorder) severity at post treatment was none. Diagnostic results (unless otherwise stated, normal values were not provided):  On an unknown date, Anti-thyroid antibody result was positive unknown. On an unknown date, Antinuclear antibody result was 1:40 unknown. On an unknown date, Blood thyroid stimulating hormone result was positive unknown. On an unknown date, Bush-Francis catatonia rating scale result was see text unknown. On an unknown date, C-reactive protein result was normal unknown. On an unknown date, CSF cell count result was normal unknown. On an unknown date, CSF glucose result was normal unknown. On an unknown date, CSF protein result was normal unknown. On an unknown date, Electroencephalogram result was normal unknown. On an unknown date, Nuclear magnetic resonance imaging result was normal unknown. On an unknown date, Red blood cell sedimentation rate result was normal unknown.  Additional information was provided.  This case was reported in a literature article and described the occurrence of Down syndrome disintegrative disorder, acute onset insomnia; autistic characteristics, catatonic symptoms, cognitive decline, hallucinations in a 17-years old female patient, who was vaccinated with unspecified influenza vaccine (manufacturer unknown) for prophylaxis. This case corresponds to patient 1 reported in this literature article.  At the age of 7-years, the patient was diagnosed with Grave's disease with positive-titer thyroperoxidase antibodies and was treated with radioisotope thyroid ablation followed by chronic hormone replacement. The patient had subsequent antibody seronegativity. The patient was social, with mild intellectual disability. The patient was able to perform all activities of daily living and did well in school. The patient had Down syndrome with a history of acute or subacute cognitive decline that was identified by physician in the Down syndrome clinic between 2014 and 2016. The onset of symptoms was after the age of 10 years and was treated with immunotherapy. The patient had a history of autoimmunity. The patient was seronegative at the onset of Down syndrome disintegrative disorder (DSDD) symptoms. No information on patient's family history and concomitant medication were provided.  On an unspecified date, the patient received unspecified influenza vaccine (administration route and site unspecified; dosage unknown; batch number not provided). The age of patient could be 16 or 17 years.  On an unspecified date, at the age of 17-years, 2 weeks after an influenza immunization, the patient developed acute onset insomnia followed by autistic characteristics, catatonic symptoms (severe symptoms included stupor, staring, posturing, stereotypy, verbigeration, rigidity, withdrawal, perseveration and mild symptoms included mutism, echolalia, mannerisms, combativeness), cognitive decline, hallucinations. The patient's intelligence quotient (IQ) was decreased from 70 to 32. She became unable to read and perform activities of daily living and was incontinent of urine and stool. The patient's BFCRS (Bush-Francis Catatonia Rating Scale) out of 54 at baseline was 1, at pretreatment was 30. The AIS (Athens Insomnia Scale) out of 24, at baseline was 0, at pretreatment was 20. The ASD (Autism spectrum disorder) severity at baseline was none, at pretreatment was moderate. The patient was hospitalised for 3 months and treated for psychosis with haloperidol, fluoxetine, and lurasidone. The patient's comorbid diagnosis was positive for cognitive decline, catatonia, autism, insomnia, psychosis and seizures. The patient's condition stabilized, and these medications were gradually discontinued. The patient slowly recovered over the next several months. The episode lasted 8 months in total. On an unspecified date, the patient again received unspecified influenza vaccine (administration route and site unspecified; dosage unknown; batch number not provided). Age of vaccination was not provided. On an unspecified date, at the age of 19-years, an unknown period after vaccination, the patient had a second episode consisting of sudden-onset, severe insomnia, cognitive and language decline, and catatonia. There were no apparent psychological stressors. There was no report of newly diagnosed sleep apnea surrounding the onset of symptoms. The patient was admitted to the hospital where she had a seizure. The patient had normal electroencephalogram (EEG). Magnetic resonance imaging (MRI) and cerebrospinal fluid studies (cell count, glucose, protein) were also normal. The oligoclonal bands and autoimmune encephalitis (AE) panel (CSF AE panel included N-methyl-D-aspartate, glutamic acid decarboxylase 65, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, gamma-aminobutyric acid receptor B subunit, collapsin response-mediator protein-5, amphiphysin, leucine-rich, glioma-inactivated 1, contactin-associated protein 2, voltage-gated potassium channel, antineuronal nuclear antibody 1, antineuronal nuclear antibody 2, antineuronal nuclear antibody 3, antiglial nuclear antibody, purkinje cell cytoplasmic antibody 1, 2, and Tr) was negative. The serum thyroid antibody showed thyroperoxidase (TPO), thyroid stimulating hormone (TSH) and microsomal (positive for all). The antinuclear antibody (ANA) was 1:40, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) was normal. The autoimmune encephalitis (AE) panel (serum AE panel included above plus striational, N-type calcium channel, P/Q type calcium channel, and acetylcholine receptor) was negative. The patient had documented auto-antibodies. Her catatonia did not respond to lorazepam. At the age of 20 years, the patient was treated with high dose methylprednisolone 1 week after the onset of symptoms (1000mg daily for 3 days and 1000mg once 1 month later), resulting in prompt and dramatic improvement. Within 1 month, the patient developed steroid induced myopathy, so patient was transitioned to monthly intravenous immunoglobulin (IVIG) (2g/kg for 1 month, then 1g/kg monthly for 18 month). Time to immunotherapy was less than 1 month. Time to significant improvement in symptoms was immediate (time to improvement from initiation of therapy was based on physician documentation in the patient record). Time to peak improvement was 2-3 months. The mycophenolate (500mg BID-twice a day for 3 month) was started and then discontinued because of cytopenia. The patient's BFCRS post treatment was 0. The AIS (Athens Insomnia Scale) out of 24, at post treatment was 1. The ASD (Autism spectrum disorder) severity at post treatment was none. She had a robust response to IVIG, fully regaining and even surpassing previous capabilities, with complete resolution of her catatonia, autism, insomnia, and seizures. Initial attempts to gradually discontinue IVIG resulted in relapse. After 18 months, the IVIG was discontinued successfully and she had no residual symptoms. There was otherwise no evidence of inflammation in the patient. The patient was reported as a part of retrospective, descriptive case series that presented the response to immunotherapy in a small cohort of patients with DSDD who had evidence of autoimmunity. It was reported that because patient did not have symptoms of sleep apnea, sleep studies were not performed and this comorbid diagnosis may have been missed.  This case has been considered as serious due to hospitalisation.  The patient had improvement in overall function as well as in all above-mentioned symptom domains within weeks after immunotherapy.  The authors did not comment on the relationship between the event of insomnia, autistic characteristics, catatonic symptoms, cognitive decline, hallucinations, seizures and unspecified seasonal influenza vaccine. The authors stated, "This supports the hypothesis that, in some patients, DSDD is immunemediated. Immunotherapy should be considered in the treatment of DSDD, particularly in patients with a history of autoimmunity. These patients may have a dysregulated immune system which predisposed them to both autoinflammatory disease and encephalopathy".  The authors concluded, "immunotherapy may be of benefit to some patients with DSDD, but further prospective study is recommended to clarify response and selection of immunotherapy candidates".      Lab Comments: Lab tests were performed on unspecified dates. The patient's BFCRS (Bush-Francis Catatonia Rating Scale) out of 54 at baseline was 1, at pretreatment was 30. The AIS (Athens Insomnia Scale) out of 24, at baseline was 0, at pretreatment was 20. The ASD (Autism spectrum disorder) severity at baseline was none, at pretreatment was moderate. The oligoclonal bands and autoimmune encephalitis (AE) panel (CSF AE panel) included N-methyl-D-aspartate, glutamic acid decarboxylase 65, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, gamma-aminobutyric acid receptor B subunit, collapsin response-mediator protein-5, amphiphysin, leucine-rich, glioma-inactivated 1, contactin-associated protein 2, voltage-gated potassium channel, antineuronal nuclear antibody 1, antineuronal nuclear antibody 2, antineuronal nuclear antibody 3, antiglial nuclear antibody, purkinje cell cytoplasmic antibody 1, 2, and Tr) was negative. The serum thyroid antibody showed microsomal positive. The autoimmune encephalitis (AE) panel (serum AE panel included above plus striational, N-type calcium channel, P/Q type calcium channel, and acetylcholine receptor) was negative. The patient had documented auto-antibodies. The patient's BFCRS post treatment was 0. The AIS (Athens Insomnia Scale) out of 24, at post treatment was 1. The ASD (Autism spectrum disorder) severity at post treatment was none.