olly
Extremely helpful member
- Joined
- Jan 10, 2008
- Messages
- 2,743
- Reason
- PALS
- Diagnosis
- 11/2007
- Country
- uk
- State
- uk
- City
- uk
By the mid-1990s there had been more or lessa consensus view that PLS could be recognizedclinically if the other conditions were excluded, that thesyndrome was more slowly progressive than ALS itself,that it was almost never familial or associated withdementia, and that onset was after age 40. Zhai et al[30] concluded that in most patients, symptoms startedwith spastic paraplegia, but a substantial minority beganwith bulbar or upper limb symptoms. Yet some patientsdeveloped lower motor neuron signs more than 25 yearsafter symptom-onset [31] and some authoritiesconcluded that PLS was merely another form of ALS(in parallel with the view that PMA is a form of ALS)[32-34]. There was another problem. The evidence forthe ”consensus” view of PLS was provided by only 22autopsies that had anteceded recognition of theimportance of Bunina and ubiquitinated inclusions. By the time of the Siddique meeting in June 2004,there had been 5 reports of postmortem examinationsthat included search for the inclusions [35]. All camefrom Japan and in all cases the major disability wascaused by upper motor neuron disorder. Two had PLSplus parkinsonism and two had PLS with dementia,all atypical. Only one of the six had no inclusions andsome had visible but not prominent fasciculations. Ifthe inclusions define ALS, then those patients hadResearch advances in ALSPathologyTau-positive inclusionsA. Pick disease: tau (+) argyrophilic neuronal inclusions. B. FTDP-17: tau (+) neuronal and astrocytic inclusions with tau mutations. C. Corticobasal degeneration: tau (+) astrocytic plaques,ballooned achromatic neurons. D. Argyrophilic grain disease: tau (+) inclusions react with silver stains. Tau-negative inclusions1. FTD-MND: tau (-), ubiquitin (+) inclusions in dentate,brainstem motor nuclei. 2. Dementia lacking distinctive histology. Clinical featuresA. Frontal, behavioral type: personality change, disinhibition, loss of empathy, eating disorders, ritual or stereotypic behavior, apathy.B. Primary progressive aphasia; fluent (temporal pathology,semantic dementia) or non-fluent (primarily frontal pathology,perisylvian). C. Either (A) or (B) with motor neuron disease. D. Overlap with corticobasal degeneration. Table 4. Clinicopathological classification of frontotemporal dementia fromHodges et al [19]
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Neurologia i Neurochirurgia Polska 2005; 39, 16Lewis P. RowlandALS, not PLS. Even the one case lacking inclusionscannot be taken as defining PLS because finding theseelusive structures depends on how many neuronsremain and how patient the pathologist can be inlooking for sparse structures. Nevertheless, 3 of the5 cases lived more than 7 years and prospective studiesare needed to determine whether UMN-dominantALS progresses more slowly than more typical ALS.(In ”UMN-dominant ALS”, corticospinal signs areevident and LMN signs are restricted to fasciculationin the tongue without major bulbar symptoms or smallmuscles of the hand without functional handicap). 4. Alsin and other genes affect definitions of ALS,PLS, and hereditary spastic paraplegiaIn 1990, Ben Hamida et al [36], in Tunisia,described three then-new forms of familial motorneuron disease in adolescents: juvenile ALS with bothupper and lower motor neuron signs; spastic paraplegiawith peroneal muscular atrophy; and a spastic syndromewith pseudobulbar symptoms. Some cases were familial,others sporadic. Then, Gascon et al [37] describedwhat they called ”childhood PLS with gaze paresis”;onset was in late infancy. The Tunisian investigatorssoon teamed with Pericak-Vance at Duke to map theautosomal recessive ALS type 2 to 2q33-q35 [38]. In2001, two teams of investigators [39,40] identified thegene as alsin, a quinine nucleotide exchange factor.Remarkably, the same mutations caused ALS2 (withcombined UMN and LMN signs) and also purelyUMN syndromes of PLS.
Primary Lateral Sclerosis (PLS) is defined by the presence of UMN without LMN signs. Throughout the clinical course some patients may never develop LMN signs. Often, however, LMN signs do eventually develop. If so the name is changed to UMN onset ALS. There is little doubt that the early appearance of prominent lower motor neuron (LMN) signs in a patient previously found to have a pure upper motor neuron (UMN) syndrome is a poor prognostic factor. The question still remains when, if ever, to draw a line between UMN-predominant ALS and PLS. Thus we would like to know whether analysis of the data acquired from periodic clinical and electrophysiological testing of patients who initially presented with an UMN syndrome (eventually diagnosed as having either PLS or ALS) allows an approximation of "time to LMN involvement"
i will try to find more
caroline
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Page 4
Neurologia i Neurochirurgia Polska 2005; 39, 16Lewis P. RowlandALS, not PLS. Even the one case lacking inclusionscannot be taken as defining PLS because finding theseelusive structures depends on how many neuronsremain and how patient the pathologist can be inlooking for sparse structures. Nevertheless, 3 of the5 cases lived more than 7 years and prospective studiesare needed to determine whether UMN-dominantALS progresses more slowly than more typical ALS.(In ”UMN-dominant ALS”, corticospinal signs areevident and LMN signs are restricted to fasciculationin the tongue without major bulbar symptoms or smallmuscles of the hand without functional handicap). 4. Alsin and other genes affect definitions of ALS,PLS, and hereditary spastic paraplegiaIn 1990, Ben Hamida et al [36], in Tunisia,described three then-new forms of familial motorneuron disease in adolescents: juvenile ALS with bothupper and lower motor neuron signs; spastic paraplegiawith peroneal muscular atrophy; and a spastic syndromewith pseudobulbar symptoms. Some cases were familial,others sporadic. Then, Gascon et al [37] describedwhat they called ”childhood PLS with gaze paresis”;onset was in late infancy. The Tunisian investigatorssoon teamed with Pericak-Vance at Duke to map theautosomal recessive ALS type 2 to 2q33-q35 [38]. In2001, two teams of investigators [39,40] identified thegene as alsin, a quinine nucleotide exchange factor.Remarkably, the same mutations caused ALS2 (withcombined UMN and LMN signs) and also purelyUMN syndromes of PLS.
Primary Lateral Sclerosis (PLS) is defined by the presence of UMN without LMN signs. Throughout the clinical course some patients may never develop LMN signs. Often, however, LMN signs do eventually develop. If so the name is changed to UMN onset ALS. There is little doubt that the early appearance of prominent lower motor neuron (LMN) signs in a patient previously found to have a pure upper motor neuron (UMN) syndrome is a poor prognostic factor. The question still remains when, if ever, to draw a line between UMN-predominant ALS and PLS. Thus we would like to know whether analysis of the data acquired from periodic clinical and electrophysiological testing of patients who initially presented with an UMN syndrome (eventually diagnosed as having either PLS or ALS) allows an approximation of "time to LMN involvement"
i will try to find more
caroline