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Progressive sclerosing poliodystrophy(MTDPS4A)

MedGen UID:
60012
Concept ID:
C0205710
Disease or Syndrome
Synonyms: Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis; Alpers disease; Alpers progressive infantile poliodystrophy; Alpers Syndrome; Alpers-Huttenlocher Syndrome; Diffuse cerebral degeneration in infancy; Infantile poliodystrophy; Mitochondrial DNA Depletion Syndrome 4A; Mitochondrial DNA depletion syndrome 4A (Alpers type); MTDPS4A; Neuronal degeneration of childhood with liver disease, progressive; Poliodystrophia cerebri progressiva; Progressive cerebral poliodystrophy
SNOMED CT: Progressive neuronal degeneration with liver cirrhosis (20415001); Alper's disease (20415001); Progressive sclerosing poliodystrophy (20415001); Alpers' disease (20415001); Gray matter degeneration (20415001); Spongy glioneuronal dystrophy (20415001); Poliodystrophy (20415001)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): POLG (15q26.1)
 
Monarch Initiative: MONDO:0008758
OMIM®: 203700
Orphanet: ORPHA726

Definition

POLG-related disorders comprise a continuum of overlapping phenotypes that were clinically defined long before their molecular basis was known. Most affected individuals have some, but not all, of the features of a given phenotype; nonetheless, the following nomenclature can assist the clinician in diagnosis and management. Onset of the POLG-related disorders ranges from infancy to late adulthood. Alpers-Huttenlocher syndrome (AHS), one of the most severe phenotypes, is characterized by childhood-onset progressive and ultimately severe encephalopathy with intractable epilepsy and hepatic failure. Childhood myocerebrohepatopathy spectrum (MCHS) presents between the first few months of life and about age three years with developmental delay or dementia, lactic acidosis, and a myopathy with failure to thrive. Other findings can include liver failure, renal tubular acidosis, pancreatitis, cyclic vomiting, and hearing loss. Myoclonic epilepsy myopathy sensory ataxia (MEMSA) now describes the spectrum of disorders with epilepsy, myopathy, and ataxia without ophthalmoplegia. MEMSA now includes the disorders previously described as spinocerebellar ataxia with epilepsy (SCAE). The ataxia neuropathy spectrum (ANS) includes the phenotypes previously referred to as mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO). About 90% of persons in the ANS have ataxia and neuropathy as core features. Approximately two thirds develop seizures and almost one half develop ophthalmoplegia; clinical myopathy is rare. Autosomal recessive progressive external ophthalmoplegia (arPEO) is characterized by progressive weakness of the extraocular eye muscles resulting in ptosis and ophthalmoparesis (or paresis of the extraocular muscles) without associated systemic involvement; however, caution is advised because many individuals with apparently isolated arPEO at the onset develop other manifestations of POLG-related disorders over years or decades. Of note, in the ANS spectrum the neuropathy commonly precedes the onset of PEO by years to decades. Autosomal dominant progressive external ophthalmoplegia (adPEO) typically includes a generalized myopathy and often variable degrees of sensorineural hearing loss, axonal neuropathy, ataxia, depression, parkinsonism, hypogonadism, and cataracts (in what has been called "chronic progressive external ophthalmoplegia plus," or "CPEO+"). [from GeneReviews]

Additional descriptions

From OMIM
Mitochondrial DNA depletion syndrome-4A, also known as Alpers syndrome, is an autosomal recessive disorder characterized by a clinical triad of psychomotor retardation, intractable epilepsy, and liver failure in infants and young children. Pathologic findings include neuronal loss in the cerebral gray matter with reactive astrocytosis and liver cirrhosis. The disorder is progressive and often leads to death from hepatic failure or status epilepticus before age 3 years (review by Milone and Massie, 2010). Some affected individuals may show mild intermittent 3-methylglutaconic aciduria and defects in mitochondrial oxidative phosphorylation (Wortmann et al., 2009). For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). Neuropathologic changes characteristic of Alpers syndrome, namely laminar cortical necrosis, may also be seen in some patients with combined oxidative phosphorylation deficiency-14 (COXPD14; 614946), caused by mutation in the FARS2 gene (611592), and COXPD24 (616239), caused by mutation in the NARS2 gene (612803).  http://www.omim.org/entry/203700
From MedlinePlus Genetics
Alpers-Huttenlocher syndrome is one of the most severe of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. Alpers-Huttenlocher syndrome typically becomes apparent in children between ages 2 and 4. People with this condition usually have three characteristic features: recurrent seizures that do not improve with treatment (intractable epilepsy), loss of mental and movement abilities (psychomotor regression), and liver disease.

People with Alpers-Huttenlocher syndrome usually have additional signs and symptoms. Most have problems with coordination and balance (ataxia) and disturbances in nerve function (neuropathy). Neuropathy can lead to abnormal or absent reflexes (areflexia). In addition, affected individuals may develop weak muscle tone (hypotonia) that worsens until they lose the ability to control their muscles and movement. Some people with Alpers-Huttenlocher syndrome lose the ability to walk, sit, or feed themselves. Other movement-related symptoms in affected individuals can include involuntary muscle twitches (myoclonus), uncontrollable movements of the limbs (choreoathetosis), or a pattern of movement abnormalities known as parkinsonism.

Affected individuals may have other brain-related signs and symptoms. Migraine headaches, often with visual sensations or auras, are common. Additionally, people with this condition may have decreased brain function that is demonstrated as sleepiness, inability to concentrate, irritability, or loss of language skills or memory. Some people with the condition may lose their eyesight or hearing. People with Alpers-Huttenlocher syndrome can survive from a few months to more than 10 years after the condition first appears.  https://medlineplus.gov/genetics/condition/alpers-huttenlocher-syndrome
From MedlinePlus Genetics
Childhood myocerebrohepatopathy spectrum, commonly called MCHS, is part of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. MCHS typically becomes apparent in children from a few months to 3 years old. People with this condition usually have problems with their muscles (myo-), brain (cerebro-), and liver (hepato-).

Common signs and symptoms of MCHS include muscle weakness (myopathy), developmental delay or a deterioration of intellectual function, and liver disease. Another possible sign of this condition is a toxic buildup of lactic acid in the body (lactic acidosis). Often, affected children are unable to gain weight and grow at the expected rate (failure to thrive).

Additional signs and symptoms of MCHS can include a form of kidney disease called renal tubular acidosis, inflammation of the pancreas (pancreatitis), recurrent episodes of nausea and vomiting (cyclic vomiting), or hearing loss.  https://medlineplus.gov/genetics/condition/childhood-myocerebrohepatopathy-spectrum

Clinical features

From HPO
Aciduria
MedGen UID:
488840
Concept ID:
C0278026
Finding
Excretion of urine with an acid pH, i.e., having an increased hydrogen ion concentration.
Ethylmalonic aciduria
MedGen UID:
355967
Concept ID:
C1865353
Finding
The concentration of ethylmalonic acid in the urine, normalized for urine concentration, is above the upper limit of normal.
3-Methylglutaconic aciduria
MedGen UID:
777186
Concept ID:
C3696376
Disease or Syndrome
An increased amount of 3-methylglutaconic acid in the urine.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Ascites
MedGen UID:
416
Concept ID:
C0003962
Disease or Syndrome
Accumulation of fluid in the peritoneal cavity.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Liver failure
MedGen UID:
88444
Concept ID:
C0085605
Disease or Syndrome
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.
Acute liver failure
MedGen UID:
58125
Concept ID:
C0162557
Disease or Syndrome
Hepatic failure refers to the inability of the liver to perform its normal synthetic and metabolic functions, which can result in coagulopathy and alteration in the mental status of a previously healthy individual. Hepatic failure is defined as acute if there is onset of encephalopathy within 8 weeks of the onset of symptoms in a patient with a previously healthy liver.
Micronodular cirrhosis
MedGen UID:
75640
Concept ID:
C0267812
Disease or Syndrome
A type of cirrhosis characterized by the presence of small regenerative nodules.
Bile duct proliferation
MedGen UID:
120603
Concept ID:
C0267818
Disease or Syndrome
Proliferative changes of the bile ducts.
Microvesicular hepatic steatosis
MedGen UID:
376784
Concept ID:
C1850415
Finding
A form of hepatic steatosis characterized by the presence of small, lipid-laden vesicles in the affected hepatocytes.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Gliosis
MedGen UID:
4899
Concept ID:
C0017639
Pathologic Function
Gliosis is the focal proliferation of glial cells in the central nervous system.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
Epilepsia partialis continua
MedGen UID:
39303
Concept ID:
C0085543
Disease or Syndrome
Epilepsia partialis continua (also called Kojevnikov's or Kozhevnikov's epilepsia) is a type of focal motor status epilepticus characterized by repeated stereotyped simple motor manifestations such as jerks, typically of a limb or the face, recurring every few seconds or minutes for extended periods (days or years).
Encephalopathy
MedGen UID:
39314
Concept ID:
C0085584
Disease or Syndrome
Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Tetraparesis
MedGen UID:
78731
Concept ID:
C0270790
Finding
Weakness of all four limbs.
Generalized non-convulsive status epilepticus without coma
MedGen UID:
124372
Concept ID:
C0270823
Disease or Syndrome
Generalized non-convulsive status epilepticus without coma is a type of status epilepticus without prominent motor signs, which is electrographically generalized. It is a prolonged absence seizure.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Abnormality of visual evoked potentials
MedGen UID:
105509
Concept ID:
C0522214
Finding
An anomaly of visually evoked potentials (VEP), which are electrical potentials, initiated by brief visual stimuli, which are recorded from the scalp overlying the visual cortex.
Paralysis
MedGen UID:
105510
Concept ID:
C0522224
Finding
Paralysis of voluntary muscles means loss of contraction due to interruption of one or more motor pathways from the brain to the muscle fibers. Although the word paralysis is often used interchangeably to mean either complete or partial loss of muscle strength, it is preferable to use paralysis or plegia for complete or severe loss of muscle strength, and paresis for partial or slight loss. Motor paralysis results from deficits of the upper motor neurons (corticospinal, corticobulbar, or subcorticospinal). Motor paralysis is often accompanied by an impairment in the facility of movement.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Vegetative state
MedGen UID:
182977
Concept ID:
C0917808
Pathologic Function
The absence of wakefulness and consciousness, but in contrast to a coma, there is involuntary opening of the eyes and movements such as teeth grinding, yawning, or thrashing of the extremities.
Increased CSF protein concentration
MedGen UID:
329971
Concept ID:
C1806780
Finding
Increased concentration of protein in the cerebrospinal fluid.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Neuronal loss in central nervous system
MedGen UID:
342515
Concept ID:
C1850496
Finding
Cerebral cortical neurodegeneration
MedGen UID:
349259
Concept ID:
C1859863
Finding
Astrocytosis
MedGen UID:
854483
Concept ID:
C3887640
Pathologic Function
Proliferation of astrocytes in the area of a lesion of the central nervous system.
Focal myoclonic seizure
MedGen UID:
869083
Concept ID:
C4023501
Disease or Syndrome
A type of focal motor seizure characterized by sudden, brief (<100 ms) involuntary single or multiple contraction(s) of muscles(s) or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Tracheomalacia
MedGen UID:
215296
Concept ID:
C0948187
Disease or Syndrome
Congenital tracheomalacia is a rare condition where the trachea is soft and flexible causing the tracheal wall to collapse when exhaling, coughing or crying, that usually presents in infancy, and that is characterized by stridor and noisy breathing or upper respiratory infections. Tracheomalacia improves by the age of 18-24 months.
Hypoventilation
MedGen UID:
469022
Concept ID:
C3203358
Pathologic Function
A reduction in the amount of air transported into the pulmonary alveoli by breathing, leading to hypercapnia (increase in the partial pressure of carbon dioxide).
Anasarca
MedGen UID:
101794
Concept ID:
C0151603
Pathologic Function
An extreme form of generalized edema with widespread and massive edema due to effusion of fluid into the extracellular space.
Increased circulating lactate concentration
MedGen UID:
332209
Concept ID:
C1836440
Finding
Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35).
Elevated circulating hepatic transaminase concentration
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Visual loss
MedGen UID:
784038
Concept ID:
C3665386
Finding
Loss of visual acuity (implying that vision was better at a certain time point in life). Otherwise the term reduced visual acuity should be used (or a subclass of that).
Cerebral visual impairment
MedGen UID:
890568
Concept ID:
C4048268
Pathologic Function
A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVProgressive sclerosing poliodystrophy
Follow this link to review classifications for Progressive sclerosing poliodystrophy in Orphanet.

Professional guidelines

PubMed

Jolliffe EA, Guo Y, Hardy TA, Morris PP, Flanagan EP, Lucchinetti CF, Tobin WO
Neurology 2021 Jul 27;97(4):e414-e422. Epub 2021 May 19 doi: 10.1212/WNL.0000000000012230. PMID: 34011576Free PMC Article
Watkins PA, Naidu S, Moser HW
J Inherit Metab Dis 1987;10 Suppl 1:46-53. doi: 10.1007/BF01812846. PMID: 3119941
Milunsky A, Littlefield JW, Kanfer JN, Kolodny EH, Shih VE, Atkins L
N Engl J Med 1970 Dec 24;283(26):1441-7. doi: 10.1056/NEJM197012242832605. PMID: 4098222

Recent clinical studies

Etiology

Lamperti C, Zeviani M
Epileptic Disord 2016 Sep 1;18(S2):94-102. doi: 10.1684/epd.2016.0846. PMID: 27618766
Rovira Á, Auger C, Rovira A
Handb Clin Neurol 2016;135:425-446. doi: 10.1016/B978-0-444-53485-9.00021-0. PMID: 27432677
Wong LJ, Naviaux RK, Brunetti-Pierri N, Zhang Q, Schmitt ES, Truong C, Milone M, Cohen BH, Wical B, Ganesh J, Basinger AA, Burton BK, Swoboda K, Gilbert DL, Vanderver A, Saneto RP, Maranda B, Arnold G, Abdenur JE, Waters PJ, Copeland WC
Hum Mutat 2008 Sep;29(9):E150-72. doi: 10.1002/humu.20824. PMID: 18546365Free PMC Article
Martin JJ, Guazzi GC
Dev Neurosci 1991;13(4-5):267-73. doi: 10.1159/000112172. PMID: 1817032
Yatsu FM
Calif Med 1971 Apr;114(4):1-6. PMID: 5551302Free PMC Article

Diagnosis

Hardy TA, Miller DH
Lancet Neurol 2014 Jul;13(7):740-6. doi: 10.1016/S1474-4422(14)70052-3. PMID: 24943346
Saneto RP, Cohen BH, Copeland WC, Naviaux RK
Pediatr Neurol 2013 Mar;48(3):167-78. doi: 10.1016/j.pediatrneurol.2012.09.014. PMID: 23419467Free PMC Article
Wong LJ, Naviaux RK, Brunetti-Pierri N, Zhang Q, Schmitt ES, Truong C, Milone M, Cohen BH, Wical B, Ganesh J, Basinger AA, Burton BK, Swoboda K, Gilbert DL, Vanderver A, Saneto RP, Maranda B, Arnold G, Abdenur JE, Waters PJ, Copeland WC
Hum Mutat 2008 Sep;29(9):E150-72. doi: 10.1002/humu.20824. PMID: 18546365Free PMC Article
O'Neill BP, Moser HW
Can J Neurol Sci 1982 Nov;9(4):449-52. doi: 10.1017/s0317167100044383. PMID: 6758925
Yatsu FM
Calif Med 1971 Apr;114(4):1-6. PMID: 5551302Free PMC Article

Therapy

Lin CJ, Lin SC, Yu KW, Ou Yang WY, Lee YC, Liao YC
Acta Neurol Taiwan 2024 Dec 30;33(4):195-200. PMID: 38073158
Dunn-Pirio AM, Eckstein C
Mult Scler Relat Disord 2018 Nov;26:8-10. Epub 2018 Sep 5 doi: 10.1016/j.msard.2018.09.001. PMID: 30212769
Wiltshire E, Davidzon G, DiMauro S, Akman HO, Sadleir L, Haas L, Zuccollo J, McEwen A, Thorburn DR
Arch Neurol 2008 Jan;65(1):121-4. doi: 10.1001/archneurol.2007.14. PMID: 18195149
Ladenson PW
JAMA 1989 Sep 15;262(11):1504-6. PMID: 2769901
Shapira Y, Cederbaum SD, Cancilla PA, Nielsen D, Lippe BM
Neurology 1975 Jul;25(7):614-21. doi: 10.1212/wnl.25.7.614. PMID: 1171391

Prognosis

Ayrignac X, Carra-Dallière C, Labauge P
Rev Neurol (Paris) 2018 Jun;174(6):408-418. Epub 2018 Apr 16 doi: 10.1016/j.neurol.2018.03.007. PMID: 29673573
Rovira Á, Auger C, Rovira A
Handb Clin Neurol 2016;135:425-446. doi: 10.1016/B978-0-444-53485-9.00021-0. PMID: 27432677
Desguerre I, Hully M, Rio M, Nabbout R
Rev Neurol (Paris) 2014 May;170(5):375-80. Epub 2014 May 5 doi: 10.1016/j.neurol.2014.03.010. PMID: 24810279
Wong LJ, Naviaux RK, Brunetti-Pierri N, Zhang Q, Schmitt ES, Truong C, Milone M, Cohen BH, Wical B, Ganesh J, Basinger AA, Burton BK, Swoboda K, Gilbert DL, Vanderver A, Saneto RP, Maranda B, Arnold G, Abdenur JE, Waters PJ, Copeland WC
Hum Mutat 2008 Sep;29(9):E150-72. doi: 10.1002/humu.20824. PMID: 18546365Free PMC Article
Aubourg P, Scotto J, Rocchiccioli F, Feldmann-Pautrat D, Robain O
J Neurol Neurosurg Psychiatry 1986 Jan;49(1):77-86. doi: 10.1136/jnnp.49.1.77. PMID: 2420940Free PMC Article

Clinical prediction guides

Smith LA, Chen C, Lax NZ, Taylor RW, Erskine D, McFarland R
Acta Neuropathol Commun 2023 May 31;11(1):86. doi: 10.1186/s40478-023-01579-w. PMID: 37259148Free PMC Article
Jolliffe EA, Guo Y, Hardy TA, Morris PP, Flanagan EP, Lucchinetti CF, Tobin WO
Neurology 2021 Jul 27;97(4):e414-e422. Epub 2021 May 19 doi: 10.1212/WNL.0000000000012230. PMID: 34011576Free PMC Article
Wong LJ, Naviaux RK, Brunetti-Pierri N, Zhang Q, Schmitt ES, Truong C, Milone M, Cohen BH, Wical B, Ganesh J, Basinger AA, Burton BK, Swoboda K, Gilbert DL, Vanderver A, Saneto RP, Maranda B, Arnold G, Abdenur JE, Waters PJ, Copeland WC
Hum Mutat 2008 Sep;29(9):E150-72. doi: 10.1002/humu.20824. PMID: 18546365Free PMC Article
Moser HW, Naidu S, Kumar AJ, Rosenbaum AE
Crit Rev Neurobiol 1987;3(1):29-88. PMID: 3552451
Lenard HG
Neuropediatrics 1984 Sep;15 Suppl:16-9. doi: 10.1055/s-2008-1052375. PMID: 6100794

Recent systematic reviews

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