This text brings together leading authorities presenting state-of-the-art clinical reviews covering the science, recognition, and treatment of the inherited metabolic epilepsies and related disorders. [books.google.de]

They are present both in the central nervous system and in the peripheral nervous system, more specifically in the tengmentum of the brainstem and in the dorsal horns of the spinal cord (Hedley-Whyte, B., Floyd, Gilles, & Uzman, 1968, p. 891). [breathepsychology.wordpress.com]

Distinctive facial deformities may be present at birth, including a prominent forehead, crossed eyes, an unusually small nose or jaw, and large, low-set ears. [secure.ssa.gov]

Symptoms usually present between 6 and 18 months of age. There is often rapid onset of motor and intellectual regression. Diminished muscle tone, called hypotonia, is also present. Hypotonia means the infant will be weak and ‘floppy’. [raregenomics.org]

• Feeding Difficulties

  difficulties Feeding problems Poor feeding [ more ] 0011968 Frontal bossing 0002007 Gait ataxia Inability to coordinate movements when walking 0002066 Generalized hypotonia Decreased muscle tone Low muscle tone [ more ] 0001290 Generalized muscle weakness [rarediseases.info.nih.gov]

  No feeding difficulties or hypotonia were noticed. Her motion and mental development were normal at 8 months after birth. At the age of 2 months, she achieved head control. Her parents noticed the onset of nystagmus at 6 months. [spandidos-publications.com]

• Fishing

  We recommend that people with INAD or PLAN be started on an age or weight appropriate dose of DHA in the form of fish or other oil. Your doctor should recommend the dose and be part of the decision to begin this supplement. [nbiacure.org]

• Difficulty Walking

  Many children experience delayed/difficulty walking, loss of neck control and low muscle tone in the trunk, which occurs early on. Eventually, muscle tightness and weakness in both arms and legs will follow. [inadcure.org]

• Constipation

  Medication for spasticity, dystonia and/or seizures Feeding modifications to prevent aspiration pneumonia and achieve adequate nutrition Addition of gastric feeding tube or tracheostomy (if needed) Fiber supplements and/or stool softener treatment for constipation [nbiacure.org]

  […] balance -Walking difficulties: shuffling, freezing or getting stuck while walking -Involuntary muscles contractions and spasms (dystonia) – Poor articulation and speech (dysarthria) -Cold/blue hands and feet, difficulty regulating core body temperature -Constipation [rarediseases.org]

  Many individuals with NBIA have ongoing constipation due to decreased activity, diet and/or medication side-effects. Over-the-counter fiber supplements and stool softeners can often improve the discomfort. [nbiadisorders.org]

  Autonomic involvement in INAD may present as constipation or urinary incontinence [8, 22]. Indeed, nine of our patients were reported to have constipation requiring treatment, and 1 had urinary incontinence. [ojrd.biomedcentral.com]

• Choking

  This leads to nutritional problems such as Dysphagia (difficulty swallowing), difficulty chewing, choking on liquids and nasal regurgitation. Due to these challenges of eating and drinking, children are often put on feeding tubes. [inadcure.org]

  Results in speech problems Dysarthria (poor articulation or slurring) Dysphonia (defective use of the voice) Dysphasia (difficulty in using or understanding words) Causes nutritional problems Dysphagia (difficulty swallowing) Difficulty with chewing Choking [nbiacure.org]

  […] symptoms of cranial nerve dysfunction: -Speech problems including poor articulation (dysarthria), poor use of voice (dysphonia) and poor understanding of words (dysphasia) -Difficulty swallowing and chewing (dysphagia) causing nutritional problems -Choking [rarediseases.org]

  Finally, patients experience a gradual deterioration in their bulbar function, starting with choking on thin liquids or drooling (median age = 24 months, mean age = 27.8 months, range 22–39 months), progressing to inability to swallow solid food and being [ojrd.biomedcentral.com]

• Regurgitation

  This leads to nutritional problems such as Dysphagia (difficulty swallowing), difficulty chewing, choking on liquids and nasal regurgitation. Due to these challenges of eating and drinking, children are often put on feeding tubes. [inadcure.org]

  […] problems Dysarthria (poor articulation or slurring) Dysphonia (defective use of the voice) Dysphasia (difficulty in using or understanding words) Causes nutritional problems Dysphagia (difficulty swallowing) Difficulty with chewing Choking on liquids Nasal regurgitation [nbiacure.org]

  […] cranial nerve dysfunction: -Speech problems including poor articulation (dysarthria), poor use of voice (dysphonia) and poor understanding of words (dysphasia) -Difficulty swallowing and chewing (dysphagia) causing nutritional problems -Choking and nasal regurgitation [rarediseases.org]

• Low Set Ears

  Distinctive facial deformities may be present at birth, including a prominent forehead, crossed eyes, an unusually small nose or jaw, and large, low-set ears. [secure.ssa.gov]

  There are signs of Infantile Neuroaxonal Dystrophy which can be noticed at birth in some cases, including facial deformities such as crossed eyes, a small nose, large ears, low set ears, a small jaw and a jutting forehead. [disabilitybenefitscenter.org]

• Large Ears

  There are signs of Infantile Neuroaxonal Dystrophy which can be noticed at birth in some cases, including facial deformities such as crossed eyes, a small nose, large ears, low set ears, a small jaw and a jutting forehead. [disabilitybenefitscenter.org]

• Retinal Pigmentation

  The iPA 2 -VIA expression is strong in the optic nerve axons and in the cornea, moderately strong in the iris, ciliary body and lens, and very strong in the adult eye’s retinal pigment epithelium (Polster et al., 2010, p. 378). [breathepsychology.wordpress.com]

• Short Attention Span

  attention span Poor attention span Problem paying attention [ more ] 0000736 Short nose Decreased length of nose Shortened nose [ more ] 0003196 Spastic tetraplegia 0002510 Spasticity Involuntary muscle stiffness, contraction, or spasm 0001257 Strabismus [rarediseases.info.nih.gov]

• Hyperactivity

  The atypical form begins in early childhood with gait instability, ataxia, speech delay, autistic features with neurologic deterioration and extrapyramidal findings; neuropsychiatric disturbances including poor attention, hyperactivity and emotional lability [scielo.mec.pt]

  […] movements when walking 0002066 Generalized hypotonia Decreased muscle tone Low muscle tone [ more ] 0001290 Generalized muscle weakness 0003324 Gliosis 0002171 Global developmental delay 0001263 Hearing impairment Deafness Hearing defect [ more ] 0000365 Hyperactivity [rarediseases.info.nih.gov]

  […] tightness and weakness in both arms and legs -Reduced joint mobility due to muscle tightness -Overactive reflexes developing early disease -Absent reflexes developing late in disease Common neuropsychiatric symptoms: -Poor attention span -Impulsivity -Hyperactivity [rarediseases.org]

• Babinski Sign

  Infantile neuroaxonal dystrophy (INAD): Description, Causes and Risk Factors: A rare, familial disorder of early childhood manifested as progressive psychomotor deterioration, increased reflexes, Babinski sign, hypotonia and progressive blindness. [medigoo.com]

  sign 0003487 Bradykinesia Slow movements Slowness of movements [ more ] 0002067 Cerebellar atrophy Degeneration of cerebellum 0001272 Cerebral atrophy Degeneration of cerebrum 0002059 Childhood onset Symptoms begin in childhood 0011463 Chorea 0002072 [rarediseases.info.nih.gov]

  Other neurological signs that were reported in the physical examination records include positive Babinski sign in three patients, dystonia in three patients, facial dyskinesia in one patient, tongue fasciculations in one patient, dysdiadochokinesia in [ojrd.biomedcentral.com]

• Dysphasia

  Due to an impairment of the function of cranial nerves (Bulbar dysfunction), children affected by INAD often have speech problems, Dysarthria (poor articulation or slurring), Dysphonia (defective use of the voice), Dysphasia (difficulty in using or understanding [inadcure.org]

  […] connects the eye to the brain) Seen later in the disease Bulbar dysfunction (impairment of the function of cranial nerves IX, X, XI and XII) Results in speech problems Dysarthria (poor articulation or slurring) Dysphonia (defective use of the voice) Dysphasia [nbiacure.org]

  […] the nerve that connects the eye to the brain (optic atrophy) seen later in disease Common symptoms of cranial nerve dysfunction: -Speech problems including poor articulation (dysarthria), poor use of voice (dysphonia) and poor understanding of words (dysphasia [rarediseases.org]

• Cognitive Impairment

  Loss of EEG Network Efficiency Is Related to Cognitive Impairment in Dementia With Lewy Bodies. Mov Disord. 2015 Jul 16. [Medline]. Lee H, Brekelmans GJ, Roks G. [medscape.com]

• Dysmetria

  […] development Poor language development Speech and language delay Speech and language difficulties Speech delay [ more ] 0000750 Dysarthria Difficulty articulating speech 0001260 Dysdiadochokinesis Difficulty performing quick and alternating movements 0002075 Dysmetria [rarediseases.info.nih.gov]

Her extensive metabolic and hypercoagulable workup was unremarkable. She continued to have normal developmental milestones up to the age of 2 years when she started to lose her ability to sit, roll over and head control. [austinpublishinggroup.com]

• Excessive Drooling

  drooling with transdermal scopolamine patch or other treatments (as needed) Early physical therapy and orthopedic management to prevent contractures Periodic testing of vision and hearing PROGRESSION The progression of INAD is usually rapid. [nbiacure.org]

[…] disorders across the lifespan (pediatric, adult, and geriatric populations) Includes interventions and methods of treatment for the outcomes patients may experience [books.google.de]

TREATMENT There is no cure for INAD and no treatment that can stop the progress of the disease. Treatment is symptomatic and supportive. Doctors can prescribe medications for pain relief and sedation. [secure.ssa.gov]

We hope and pray for time, for his progression to be slow and for the research to grow to find treatment options for our son. Landon is such a special boy and blessing to our family. [awareofangels.org]

MANAGEMENT There is no standard treatment for INAD. Diagnosed individuals are managed by a team of medical professionals that recommends treatments based on current symptoms. [nbiacure.org]

Progression & Treatment The progression of INAD is usually rapid after the initial onset of symptoms. Many affected children never learn to walk or lose this ability shortly after learning it. [inadcure.org]

Definition Treatment Prognosis Clinical Trials Organizations Publications Definition Infantile neuroaxonal dystrophy (INAD) is a rare inherited neurological disorder. [ninds.nih.gov]

[…] spasms, parkinsonism neuropsychiatric optic atrophy retinal degeneration Radiographic features will vary among the various entities, but can broadly be thought of as 3 : basal ganglia signal abnormalities cerebellar and cerebral atrophy Treatment and prognosis [radiopaedia.org]

There are atypical forms of INAD that have been recognized with onset as late as the teen-aged years; this is an even rarer condition and the prognosis or life span is not known. [raregenomics.org]

Prognosis The progression of classic INAD is usually rapid and many children never learn to walk. Severe spasticity, progressive cognitive decline and visual impairment can result in a vegetative state. [orpha.net]

They are organised into groups, and further divided into clinical, etiological or histopathological sub-types. [orpha.net]

Treatment: Due to lack of knowledge about etiology no specific treatment is available. A Rehabilitation program including physiotherapy and orthopedic management might be helpful and should be started early in the course of the disease. [medigoo.com]

Continuous EEG monitoring in comatose intensive care patients: epileptiform activity in etiologically distinct groups. Neurocrit Care. 2005. 2(1):5-10. [Medline]. Kameda K, Itoh N, Nakayama H. [medscape.com]

[…] dystrophy (NAD) aceruloplasminaemia COASY protein-associated neurodegeneration (COPAN) fatty acid hydroxylase-associated neurodegeneration (FAHN) Kufor-Rakeb syndrome neuroferritinopathy Woodhouse-Sakati syndrome No single demographic is affected, and epidemiology [radiopaedia.org]

Summary Epidemiology Prevalence is unknown, but more than 150 cases have been described, of which the majority are classic INAD. [orpha.net]

Epidemiologic trends in neonatal intensive care, 2007–2012. JAMA Pediatr. 2015;169(9):855–62. 21. Al-Wassia H, Saber MJAoSm. [ojrd.biomedcentral.com]

While understanding the pathophysiological mechanisms of PLA2G6-associated neurodegeneration is providing promising therapeutic strategies, the involvement of other cell types within the nervous system is not yet established and may be of pathophysiological [brain.oxfordjournals.org]

Pathophysiology [ edit ] Mutations in the PLA2G6 gene have been identified in most individuals with infantile neuroaxonal dystrophy. The PLA2G6 gene provides instructions for making an enzyme called an A2 phospholipase. [en.wikipedia.org]

INAD is caused by an abnormal build-up of substances in the nerves throughout the brain and body, which prevents them from working properly. [onlymyhealth.com]

[…] and/or stool softener treatment for constipation Control of secretions and excess drooling with transdermal scopolamine patch or other treatments (as needed) Early physical therapy and orthopedic management to prevent contractures Periodic testing of [nbiacure.org]

These form on the axon terminals of neurons and prevent proper nerve functioning. [breathepsychology.wordpress.com]

Currently no effective treatment isavailable.Therapeuticapproach involves treatment of manifestations for spasticity and seizures, control of secretions, prevention of aspiration pneumonia by feeding modifications, psychiatric support, prevention of secondary [scielo.mec.pt]

The main task of these therapies is to prevent development of contractures and fixed deformities. Symptomatic pharmacological treatment of spasticity and seizures with myorelaxant and antiepileptic drugs may be of some benefit. [medigoo.com]