Few detailed clinico-pathological correlations of Parkinson's disease have been published. The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported. Seventy six had nigral Lewy bodies, and in all of these Lewy bodies were also found in the cerebral cortex. In 24 cases without Lewy bodies, diagnoses included progressive supranuclear palsy, multiple system atrophy, Alzheimer's disease, Alzheimer-type pathology, and basal ganglia vascular disease. The retrospective application of recommended diagnostic criteria improved the diagnostic accuracy to 82%. These observations call into question current concepts of Parkinson's disease as a single distinct morbid entity.

https://jnnp.bmj.com/content/jnnp/55/3/181.full.pdf

Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.

Staging of brain pathology related to sporadic Parkinson’s disease

The micro-architecture of the substantia nigra was studied in control cases of varying age and patients with parkinsonism. A single 7 mu section stained with haematoxylin and eosin was examined at a specific level within the caudal nigra using strict criteria. The pars compacta was divided into a ventral and a dorsal tier, and each tier was further subdivided into 3 regions. In 36 control cases there was a linear fallout of pigmented neurons with advancing age in the pars compacta of the caudal substantia nigra at a rate of 4.7% per decade. Regionally, the lateral ventral tier was relatively spared (2.1% loss per decade) compared with the medial ventral tier (5.4%) and the dorsal tier (6.9%). In 20 Parkinson's disease (PD) cases of varying disease duration there was an exponential loss of pigmented neurons with a 45% loss in the first decade. Regionally, the pattern was opposite to ageing. Loss was greatest in the lateral ventral tier (average loss 91%) followed by the medial ventral tier (71%) and the dorsal tier (56%). The presymptomatic phase of PD from the onset of neuronal loss was estimated to be about 5 yrs. This phase is represented by incidental Lewy body cases: individuals who die without clinical signs of PD or dementia, but who are found to have Lewy bodies at post-mortem. In 7 cases cell loss was confined to the lateral ventral tier (average loss 52%) congruent with the lateral ventral selectivity of symptomatic PD. It was calculated that at the onset of symptoms there was a 68% cell loss in the lateral ventral tier and a 48% loss in the caudal nigra as a whole. The regional selectivity of PD is relatively specific. In 15 cases of striatonigral degeneration the distribution of cell loss was similar, but the loss in the dorsal tier was greater than PD by 21%. In 14 cases of Steele-Richardson-Olszewski syndrome (SRO) there was no predilection for the lateral ventral tier, but a tendency to involve the medial nigra and spare the lateral. These findings suggest that age-related attrition of pigmented nigral cells is not an important factor in the pathogenesis of PD.

Ageing and parkinson's disease: substantia nigra regional selectivity

Handbook of psychopharmacology

The clinical diagnosis of Parkinson disease (PD) is based on the identification of some combination of the cardinal motor signs of bradykinesia, rigidity, tremor, and postural instability, but few attempts have been made to develop explicit diagnostic criteria. We propose a clinical diagnostic classification based on a comprehensive review of the literature regarding the sensitivity and specificity of the characteristic clinical features of PD. Three levels of diagnostic confidence are differentiated: Definite, Probable, and Possible. The diagnoses of Possible and Probable PD are based on clinical criteria alone. Neuropathologic confirmation is required for the diagnosis of Definite PD in patients with the clinical diagnosis of Possible or Probable PD. Criteria for histopathologic confirmation of PD are also presented.

https://jamanetwork.com/journals/NEUR/articlepdf/774675/nsa7701.pdf

Diagnostic Criteria for Parkinson Disease

PARKINSONISM, described in its entirety over one hundred and fifty years ago,’ rarely presents itself as a diagnostic problem. In consequence, little scrutiny has been directed to the marked variability of this frequently encountered neurological syndrome and to the progression of the disease in large groups of patients. As with most chronic neurological disorders, marked diversity can be expected to exist in age and mode of onset, relative prominence of the cardinal signs and symptoms, rate of progression, and resultant degree of functional impairment. Controversy over the effectiveness of therapeutic measures for parkinsonism is due partially to this wide variability and to the paucity of clinical information about the natural history of the syndrome. It is also re-

https://n.neurology.org/content/neurology/17/5/427.full.pdf

Parkinsonism: Onset, progression, and mortality

Some turn this sickness yet might take, Even yet. But he: "What drug can make A wither'd palsy cease to shake?" "The Two Voices" —Tennyson 1833 FOR MORE than a century, the treatment of parkinsonism has relied on a variety of compounds whose limited therapeutic efficacy depend upon their central parasympatholytic effects. The shortcomings of these agents, notably their inability to completely reverse the signs and symptoms or materially alter the progressive disabling nature of the disorder and the high incidence of disturbing side effects, are well appreciated. Under the most optimal circumstances, the best that can be expected from their judicious administration is a 20% reduction in the severity of symptoms with a modest improvement of functional capacity. The demonstration within the past decade of the presence of dopamine in the brain localized chiefly in the striatum and substantia nigra 1,2 and the subsequent discovery of its depletion

Treatment of parkinsonism with levodopa.

Objectives To assess long term (24 months) effects of the Lee Silverman voice treatment (LSVT), a method designed to improve vocal function in patients with Parkinson's disease. Methods Thirty three patients with idiopathic Parkinson's disease were stratified and randomly assigned to two treatment groups. One group received the LSVT, which emphasises high phonatory-respiratory effort. The other group received respiratory therapy (RET), which emphasises high respiratory effort alone. Patients in both treatment groups sustained vowel phonation, read a passage, and produced a monologue under identical conditions before, immediately after, and 24 months after speech treatment. Change in vocal function was measured by means of acoustic analyses of voice loudness (measured as sound pressure level, or SPL) and inflection in voice fundamental frequency (measured in terms of semitone standard deviation, or STSD). Results The LSVT was significantly more effective than the RET in improving (increasing) SPL and STSD immediately post-treatment and maintaining those improvements at 2 year follow up. Conclusions The findings provide evidence for the efficacy of the LSVT as well as the long term maintenance of these effects in the treatment of voice and speech disorders in patients with idiopathic Parkinson's disease.

https://jnnp.bmj.com/content/jnnp/71/4/493.full.pdf

Intensive voice treatment (LSVT®) for patients with Parkinson's disease: a 2 year follow up

The purpose of this study was to evaluate the long-term (12 months) effects of two forms of speech treatment on the speech and voice deficits that occur in Parkinson's disease. Thirty-five patients with idiopathic Parkinson's disease were assigned to one of two speech treatment groups: voice and respiration (The Lee Silverman Voice Treatment [LSVT]) or placebo (respiration) treatment. Vocal intensity data from before, immediately after, and at 6 and 12 months after speech treatment revealed statistically significant differences between the treatment groups. Only subjects in the LSVT group improved or maintained vocal intensity above pretreatment levels by 12 months after treatment. The placebo group had statistically significant deterioration of vocal intensity levels from before to 12 months after treatment during conversational monologue. The LSVT group did not deteriorate to levels below pretreatment in vocal intensity over the 12-month period. This study is the first to document the short-and long-term effects of intensive speech treatment (LSVT), which focuses on the voice, for patients with Parkinson's disease compared with a placebo speech treatment group.

Margaret M. Hoehn

Papers

Parkinsonism: Onset, progression, and mortality

Treatment of parkinsonism with levodopa.

Intensive voice treatment (LSVT®) for patients with Parkinson's disease: a 2 year follow up

Intensive speech treatment for patients with Parkinson's disease Short- and long-term comparison of two techniques

Parkinsonism: Alterations in spatial orientation as determined by a route-walking test