A female patient presented with significant developmental delay in early childhood and subsequently demonstrated neurodegeneration with progressive dystonia and dementia in her third decade. [ncbi.nlm.nih.gov]

BPAN commonly presents as global developmental delay in childhood with rapid onset of parkinsonism and dementia in early adulthood and associated pathognomonic changes seen on brain MRI. [pediatrics.aappublications.org]

• Feeding Difficulties

  Occupational therapy may aid in writing, feeding, grooming, and dressing. For those with feeding difficulties, feeding therapy may be considered. [ncbi.nlm.nih.gov]

• Bruxism

  These features include repeated hand wringing or clasping (stereotypic hand movements); teeth grinding (bruxism); sleep disturbances; and problems with communication and social interaction characteristic of autism spectrum disorder. [elbiruniblogspotcom.blogspot.no]

  […] progressive loss of cognitive function beginning in adolescence or early adulthood Progressive parkinsonism and dystonia, beginning in adolescence or early adulthood Abnormal behaviors that overlap with Rett syndrome, including stereotypic hand movements, bruxism [ncbi.nlm.nih.gov]

• Hirsutism

  At 14 years of age, she was noted to have limited elbow extension, mild hirsutism and tapering of her fingers ( Figure 1 ; Supplementary Video ). A brain MRI at that time revealed iron deposition in the basal ganglia. [nature.com]

• Hip Dislocation

  Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation). [ncbi.nlm.nih.gov]

• Abnormal Eye Movement

  She developed abnormal eye movements and auditory inattention. There were no seizures. There was no family history of neurological disease. On examination, her head circumference was normal and she did not have any dysmorphic features. [annalsofian.org]

  Torticollis is a condition in which there are involuntary contractions of neck muscles resulting in abnormal movements and positions of the head and neck. Most forms of NBIA involve eye disease. [nbiaalliance.org]

• Global Developmental Delay

  The first phase is marked by global developmental delay and seizures during early childhood. The course is dormant until adulthood, when the patient starts to develop rapidly progressing parkinsonian symptoms. [ajnr.org]

  Conclusions: BPAN is an extremely rare disease characterized by global developmental delay followed in young adulthood by progressive dystonia-parkinsonism. [neurology.org]

  Characteristic clinical features include 3 : global developmental delay during childhood sudden onset of neurocognitive changes during adolescence or young adulthood associated with levodopa resistant parkinsonism, dystonia, and dementia It was previously [radiopaedia.org]

  The natural history of their disease was remarkably uniform: global developmental delay in childhood and further regression in early adulthood with progressive dystonia, parkinsonism and dementia. [neurologiaspedalicivili.blogspot.com]

  BPAN commonly presents as global developmental delay in childhood with rapid onset of parkinsonism and dementia in early adulthood and associated pathognomonic changes seen on brain MRI. [pediatrics.aappublications.org]

• Spastic Quadriplegia

  Other clinical features include: spastic cerebral palsy spastic quadriplegia Iron accumulation in the brain specifically in globus pallidus and substantia nigra. This disorder is thought to be genetically determined with defective iron metabolism. [radiopaedia.org]

  Its clinical course is described as biphasic with an initial presentation during childhood, as spastic quadriplegia or static encephalopathy with early developmental delay with or without seizures, followed by dementia in adulthood and the development [nature.com]

• Muscle Tone Abnormalities

  Consider use of durable medical equipment as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers) For muscle tone abnormalities including hypertonia or dystonia, consider involving appropriate specialists to aid in management [ncbi.nlm.nih.gov]

• Focal Seizure

  Seizures are frequently multiform and include focal seizures with impaired consciousness, epileptic spasms [Hogarth, personal communication], and generalized seizures, including absence, atonic, myoclonic, and tonic-clonic [ Hayflick et al 2013 ]. [ncbi.nlm.nih.gov]

• Nocturnal Seizure

  Unrecognized nocturnal seizure activity may contribute to abnormal sleep patterns. Some adults with BPAN continue to have sleep difficulties or develop new manifestations such as waking and vocalizing during the night. [ncbi.nlm.nih.gov]

The youngest patient reported with these MRI findings is a 6-year-old girl with Rett syndrome–like features diagnosed by whole exome sequencing. 8 In contrast, although our patient underwent her first brain MRI as part of a diagnostic workup for cognitive [pediatrics.aappublications.org]

(See Presentation and Workup.) [4, 5, 6] PKAN is relentlessly progressive. The clinical course is characterized by progressive dementia, spasticity, rigidity, dystonia, and choreoathetosis. [emedicine.medscape.com]

• Hypsarrhythmia

  Her infantile spasms and hypsarrhythmia disappeared promptly by adrenocorticotropic hormone therapy (CORTROSYN®Z, 0.0125mg/kg/day daily for 2weeks intramuscularly), though the administration of pyridoxal phosphate and valproic acid had poor efficacy. [readbyqxmd.com]

  Early referral to a neurology epilepsy sub-specialist is recommended if hypsarrhythmia or another aggressive electrographic pattern is found on EEG. [ncbi.nlm.nih.gov]

Treatment with levodopa/carbidopa had limited effects only. Neuropsychiatric symptoms within the autistic and affective spectrum were present in the early phase of the disease. [ncbi.nlm.nih.gov]

Dopamine agonists Levodopa Deep brain stimulation Symptomatic treatment for dystonia and seizures A 33-year-old woman with a history of global developmental delay and generalized seizures in childhood presented at the age of 21 with parkinsonian symptoms [ajnr.org]

Treatment with levodopa/carbidopa was not effective.Conclusion:The neuropsychiatric phenotype of BPAN is characterized by symptoms from the autistic and anxiety spectrum that, however, shouldbe functionally interpreted as resulting form motor deterioration [docslide.com.br]

The specific course and prognosis should implicate restrained psychopharmacological interventions. The clinical picture and imaging hallmarks are often highly suggestive and should lead to suspect this specific disorder. [ncbi.nlm.nih.gov]

Early diagnosis of BPAN is of utmost importance, providing families with a direction for possible management and prognosis and preventing further unnecessary diagnostic testing. [pediatrics.aappublications.org]

(See Presentation and Prognosis.) [7, 8] The disease can be familial or sporadic. [emedicine.medscape.com]

Etiology The exact etiology of PKAN is not known. One proposed hypothesis is that abnormal peroxidation of lipofuscin to neuromelanin and deficient cysteine dioxygenase lead to abnormal iron accumulation in the brain. [emedicine.medscape.com]

Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies. Hum Mol Genet. PubMed PMID: 24973356 Guerreiro R, Wojtas A, Bras J, et al. TREM2 variants in Alzheimer's disease. N Engl J Med. [books.google.de]

Note that specific eponyms are applied to a particular clinical and electrographic profile and do not imply a specific etiology: many genetic and non-genetic etiologies can result in a given epilepsy syndrome. [ncbi.nlm.nih.gov]

[…] with brain iron accumulation type 4 - SENDA - Static encephalopathy of childhood with neurdegeneration in adulthood Classification (Orphanet): - Rare genetic disease - Rare neurologic disease Classification (ICD10): - Diseases of the nervous system - Epidemiological [csbg.cnb.csic.es]

[…] definition according to the specific consensus conference or to The Diseases Database based on the Unified Medical Language System (NLM) and a link to: a) Wikipedia definition b) The Diseases Database Also the Mesh corresponding term has to be chosen EPIDEMIOLOGY [flipper.diff.org]

Epidemiology • Estimated prevalence of 1-3/ million population has been suggested based on observed cases in a population. • PKAN: highest prevalence & founder mutation in Central Europe • Neuroferritinopathy is classically seen in patients from the Cumbrian [slideshare.net]

Beta-Propeller Protein-Associated Neurodegeneration (BPAN) •Beta-propeller protein-associated neurodegeneration is unique among the NBIAs in its mode of inheritance, its presumed pathophysiology. [slideshare.net]

Our research unit “Molecular Pathophysiology of Neurodegenerative Disorders” has investigated the molecular pathogenesis of abnormal protein accumulation in the nervous system in neurodegenerative diseases to facilitate the analyses of pathogenic substances [ura.sec.tsukuba.ac.jp]

In addition, early identification of WDR45 mutation may lead to a better understanding of the pathophysiology of BPAN and result in the development of novel therapeutic interventions for preventing or delaying the onset of neurodegeneration for pediatric [pediatrics.aappublications.org]

"Genetics and Pathophysiology of Neurodegeneration with Brain Iron Accumulation (NBIA)". primary. Current Neuropharmacology. 11 (1): 59–79. doi : 10.2174/157015913804999469. PMC 3580793. PMID 23814539. [en.wikipedia.org]

Schneider SA, Dusek P, Hardy J, Westenberger A, Jankovic J, Bhatia KP : Genetics and Pathophysiology of Neurodegeneration with Brain Iron Accumulation (NBIA). Curr Neuropharmacol 2013; 11 : 59–79. 12. [nature.com]

Currently, there is no known effective prevention or treatment of neurologic decline in BPAN. [pediatrics.aappublications.org]

It has been demonstrated that A2AR is able to prevent amyloid--induced synaptotoxicity in animal models and cell cultures. Moreover A2AR has been shown to control NMDA currents and glutamate outflow in the hippocampus. [oatd.org]

Basically, without evolution, the fledgling field of precision medicine would wither and die, and we would lose our opportunity to prevent, diagnose, and treat the diseases that account for the bulk of morbidity and mortality in humans and in animals.This [medworm.com]

To prevent him from regressing, his parents regularly work out with him. Elijah, who also helps clean at Berkshire Nautilus through his high school internship program, also exercises there. [berkshireeagle.com]

[…] dopaminergic drugs for parkinsonism for: Adverse neuropsychiatric effects Psychiatric symptoms Worsening of parkinsonism Nutrition Monitoring of height and weight in children Swallowing evaluation and regular dietary assessments Assure adequate nutrition Prevent [nbiacure.org]