Presentation
It presents most commonly in the sixth decade, but may occur any time between the third and ninth decades. Presentation Onset tends to be insidious and progression gradual. There are three main clinical syndromes of FTD. [patient.info]
Mutations in the Tau gene (known as MAPT or Microtubule Associated Protein Tau) can cause a FTLD presenting with tau pathology (FTLD-tau). [3] There are over 40 known mutations at present. [en.wikipedia.org]
RESULTS: A 63-year-old right-handed male presented with a 4-year history of insidious onset and progression of visual symptoms with mild word-finding difficulty and a right homonymous hemianopia evident on neurologic examination. [neurology.org]
The two autopsied siblings described here presented with frontotemporal dementia involving multiple cognitive domains and behavior but lacking symptoms of motor neuron disease throughout the disease course. [pesquisa.bvs.br]
Fine neurites were also present in the hippocampal CA1 region and subiculum. There were no NCIs in the cervical spinal cord, but scattered glial TDP-43 cytoplasmic inclusions were present. [academic.oup.com]
Entire Body System
- Falling
MyBioSource and its authorized distributors reserve the right to refuse to process any order where we reasonably believe that the intended use will fall outside of our acceptable guidelines. [mybiosource.com]
Progressive supranuclear palsy causes difficulties with balance and walking resulting in frequent falls. Problems with eye movements are also seen particularly an inability to look down. Changes in behavior can also occur with time. [rarediseases.org]
There is impairment of vertical gaze, postural instability, falls, behavioural change, and cognitive impairment. Corticobasal syndrome. There is asymmetric apraxia, accompanied by rigidity, myoclonus and involuntary movements of the affected side. [patient.info]
The progressive supranuclear palsy syndrome is characterised by impairment of vertical gaze, early postural instability with falls, and frontal behavioural changes with marked cognitive slowing (fronto-subcortical). 15 16 Features of corticobasal syndrome [bmj.com]
Respiratoric
- Aspiration
Death usually occurs within 3 years of onset from inanition, pulmonary failure, and aspiration. Patients with FTD/MND generally follow a more rapid course than do patients with either FTD or MND alone. [emedicine.medscape.com]
Musculoskeletal
- Myopathy
CFL2 Nemaline myopathy KBTBD13 Nemaline myopathy KLHL40 Nemaline myopathy KLHL41 Nemaline myopathy LMOD3 Severe congenital nemaline myopathy, Typical nemaline myopathy MTM1 Myopathy, centronuclear NEB Nemaline myopathy TNNT1 Nemaline myopathy TPM2 Arthrogryposis [genda.com.ar]
"VCP disease associated with myopathy, Paget disease of bone and frontotemporal dementia: review of a unique disorder". Biochim Biophys Acta. 1782 (12): 744–8. doi : 10.1016/j.bbadis.2008.09.003. PMID 18845250. ^ Borroni, B.; et al. (2010). [en.wikipedia.org]
Multisystem proteinopathy is a complex phenotype that includes FTD, Paget disease of the bone, inclusion body myopathy and MND, and can be due to mutations in VCP (valosing containing protein) and other recently identified genes. [text-br.123dok.com]
BMC Neurology 6, 44 118 Kimonis, V.E. et al. ( 2008 ) VCP disease associated with myopathy, Paget disease of bone and frontotemporal dementia: review of a unique disorder. [cambridge.org]
Acta Neuropathol 117 137-149 Olivé M, Janué A, Moreno D, Gámez J, Torrejón-Escribano B & Ferrer I 2009 TAR DNA-binding protein 43 accumulation in protein aggregate myopathies. [jmolbiochem.com]
Psychiatrical
- Distractibility
Affected people may also become easily distracted and unable to complete tasks. They increasingly require help with personal care and other activities of daily living. [ghr.nlm.nih.gov]
During the consultation, patients’ spontaneous behaviours and interactions with others are often more revealing than formal neuropsychological testing: they may be impulsive or distractible, inert or impassive, disinhibited (picking up items unbidden [bmj.com]
Changes in behavior may include a decline in personal hygiene, distractibility and hyperorality. Changes in speech and language may include echolalia and altered speech output. [unicare.com]
[…] others, including close relatives who display remarkable concerns about their health status (i.e. affective blunting).17 Besides, they become inflexible when adapting to circumstances and daily routines or distinct perspectives.18 Some might demonstrate distractibility [zdoc.site]
- Compulsive Behavior
Simple repetitive movements, continually repeating certain phrases or words, and complex ritualistic behaviors such as hoarding are examples of compulsive behaviors that can occur in individuals with behavioral variant frontotemporal degeneration. [rarediseases.org]
Six distinct clinical features have been identified as symptoms of bvFTD. [20] Disinhibition Apathy /Inertia Loss of Sympathy / Empathy Perseverative / compulsive behaviors Hyperorality Dysexecutive neuropsychological profile Of the six features, three [en.wikipedia.org]
- Compulsive Disorder
The most common subtype associated with MAPT mutations is bvFTD which may manifest as behavioral inhibition, impaired social behavior, and obsessive–compulsive disorder. [unicare.com]
Neurologic
- Cerebellar Ataxia
[…] syndrome CA8 Cerebellar ataxia, mental retardation, and dysequilibrium syndrome CACNA1A Episodic ataxia, Migraine, familial hemiplegic CACNB4 Episodic ataxia CAMTA1 Cerebellar ataxia, nonprogressive, with mental retardation CASK FG syndrome, Mental retardation [genda.com.ar]
ataxia, and cerebellar atrophy. [genecards.org]
A form of neuronal ceroid lipofuscinosis characterized by rapidly progressive visual loss due to retinal dystrophy, seizures, cerebellar ataxia, and cerebellar atrophy. Cognitive decline may also occur. [mybiosource.com]
ataxia, and ALS with multiple sclerosis.52-55 Repeat expansions in C9orf72 were also found in about 2% of patients diagnosed with Huntington-like syndrome, and this may be the most common mutation in this diagnostic group.44 he duration of symptoms is [text-br.123dok.com]
- Mild Cognitive Impairment
MAPt P301S variability * FTD phenotype and corticobasal degeneration in the same family (Bugiani et al 1999) * Parkinsonism and epileptic seizures (Sparked, 1999) * Parkinsonism followed by cognitive impairment (Kawamata, 2005) Bugiani O, Murrell JR, [docmh.net]
A case with atypical onset as clinical amnestic mild cognitive impairment converted to Alzheimer's disease. [ncbi.nlm.nih.gov]
Workup
A part of the diagnostic workup for suspected FTD includes the exclusion of other neurodegenerative conditions with similar presentations, including but not limited to Alzheimer disease. [unicare.com]
Treatment
With chapters ranging from cognitive evaluation to imaging, and genetics and pathology to treatment, the detailed clinical descriptions of diseases and symptoms serve not only as an educational tool for trainees, but also as an opportunity for experienced [books.google.com]
Treatment considerations Treatment strategies for FTD may apply to FTD/MND, but this is not known for certain. Current treatments mainly are supportive and directed toward the features of MND. [emedicine.medscape.com]
There is no cure for FTD and no treatment to prevent or delay the development of the disease. Treatment is usually focused on managing the manifestations of the disorder. [unicare.com]
There is no evidence that disease-modifying interventions have been made available so far, hence treatment remains purely symptomatic. [zdoc.site]
Treatments are available to manage the behavioral symptoms. [en.wikipedia.org]
Prognosis
Best prognosis tends to be in those with the semantic type, and survival may be as long as ten years or more. Worst prognosis is associated in the overlap syndrome with motor neurone disease, and there may only be 3-5 years between onset and death. [patient.info]
Prognosis [ edit ] Symptoms of frontotemporal dementia progress at a rapid, steady rate. Patients suffering from the disease can survive between 2–15 years. [en.wikipedia.org]
[…] results in dysphagia, the risk of aspiration pneumonia, and mutism Muscular wasting and weakness may occur Parkinsonism may develop in some patients Dyspnea and hypoxic encephalopathy may be related positionally and can interfere with reclining for sleep Prognosis [emedicine.medscape.com]
Etiology
Thus, the evidence presented here suggests that variation at rs5848 does not contribute to the etiology of FTLD in the Dutch population. [journals.plos.org]
Etiology Worldwide, frontotemporal lobe dementia with motor neuron disease (FTD/MND) is a sporadic condition with an unknown etiology. [emedicine.medscape.com]
However, much more dissections into the causative pathways are needed to get a full picture of the etiology. [annalsofian.org]
Especially, the relatively weak correlation between clinical diagnosis and underlying genetic etiologies is complicating strategies to define inclusion criteria to maximize the power of GWASs by enriching for a limited number of susceptibility genes. [neupsykey.com]
Epidemiology
Relevant External Links for GRN Genetic Association Database (GAD) GRN Human Genome Epidemiology (HuGE) Navigator GRN Atlas of Genetics and Cytogenetics in Oncology and Haematology: GRN No data available for Genatlas for GRN Gene Structure and chromosomal [genecards.org]
Heritability, however, varies with the different clinical subtypes (discussed below). [ 4 ] Epidemiology [ 5 ] FTD is much less common than Alzheimer's disease and vascular dementia. [patient.info]
Frontotemporal lobar degeneration: epidemiology, pathology, diagnosis and management. CNS Drugs 2012 ; 26 : 841 -70. ↵ Vercelletto M, Boutoleau-Bretonnière C, Volteau C, Puel M, Auriacombe S, Sarazin M, et al. [bmj.com]
Epidemiology, Diagnosis, Management and Outcomes. Drugs & Aging, 1999; 15: 81-89. [ Links ] 36. Seo SW, Thibodeau M-P, Perry DC, Hua A, Sidhu M, Sible I, et al. [scielo.org.pe]
Pathophysiology
[…] capture pathophysiological changes become available. [bmj.com]
Pathophysiology [ 1, 3 ] There is atrophy of the frontal and temporal lobes. Distribution is lobar, rather than the diffuse atrophy of Alzheimer's disease. There may be loss of neurons or gliosis but no increase in plaque formation. [patient.info]
Pathophysiological and diagnostic implications of cortical dysfunction in ALS. Nat Rev Neurol. 2016 Nov. 12 (11):651-661. [Medline]. Steele JC, McGeer PL. The ALS/PDC syndrome of Guam and the cycad hypothesis. Neurology. 2008 May 20. 70(21):1984-90. [emedicine.medscape.com]
Epidemiology, pathophysiology, diagnosis and management. CNS Drugs 2010; 24: Dickson DW. TDP-43 immunoreactivity in neurodegenerative disorders: disease versus mechanism specificity. Acta Neuropathol 2008;115: Kumar-Singh S. [docplayer.net]
Prevention
Prevention Where there is a strong family history of FTD, genetic testing should be discussed. Genetic counselling should be undertaken before testing is undertaken. [patient.info]
Most mutations in the GRN gene prevent any granulin from being produced from one copy of the gene in each cell. As a result, cells make only half the usual amount of granulin. [ghr.nlm.nih.gov]
In the meantime it remains necessary to prevent or ameliorate frequent neuropsychiatric morbidity from whatever causes. [science.gov]
There is no cure for FTD and no treatment to prevent or delay the development of the disease. Treatment is usually focused on managing the manifestations of the disorder. [unicare.com]
[…] function of PGRN or haploinsufficiency through nonsense mediated decay. [9], [10], [29] However, a limited number of mutations do not create null alleles, instead they lead to the retention and degradation of the unspliced transcript within the nucleus, preventing [annalsofian.org]