When does Parkinson's disease begin?

Pathological and neuroimaging studies have shown that in Parkinson's disease (PD) there is a “subclinical” or “premotor” period during which dopaminergic neurons in the substantia nigra (SN) degenerate but typical motor symptoms have not yet developed. Post‐mortem studies based on nigral cell counts and evaluating dopamine levels in the striata, and imaging studies assessing the nigrostriatal pathway in vivo, have estimated that this time period could last 3 to 6 years. In addition, emerging evidence indicates that the neuropathological process of PD does not start in the SN but more likely elsewhere in the nervous system: in the lower brainstem and the olfactory bulb, or even more distant from the SN, such as in the peripheral autonomic nervous system. Patients with PD frequently can present non‐motor symptoms, such as hyposmia or constipation, years before the development of classical motor signs. The physiopathology of these “premotor” symptoms, though still unclear, is currently thought to be related to early involvement by the pathological process underlying PD of non‐dopaminergic lower brainstem structures or autonomic plexuses. However, the answer to the question “when does PD start” remains uncertain. Here, we review clinical, pathological, and neuroimaging data related to the onset of the pathological process of PD, and propose that its onset is non‐motor and that non‐motor symptoms could begin in many instances 10 and 20 years before onset of motor symptoms. The variable course of the disorder once the motor symptoms develop, suggests that the start and progression of premotor PD is also highly variable andgiven the heterogeneous nature of PD, may differ depending on the cause/s of the syndrome. When and where the neuropathological process develops in PD remains uncertain. © 2009 Movement Disorder Society     

Tics in a patient with Parkinson's disease

A patient with Gilles de la Tourette syndrome later developed Parkinson's disease in middle age. This was accompanied by a marked reduction in the frequency of tics but levodopa toxicity exacerbated the tics. The dopamine hypothesis of tic disorders is supported by this observation.     

When did Ray Kennedy's Parkinson's disease begin?

Ray Kennedy's Parkinson's disease probably began during his distinguished career as a professional soccer player at least 10 years before the first unequivocal physical signs and 14 years before the diagnosis was finally made, when he was 35-years old. Early prodromal symptoms included intermittent subtle disturbances of movement and posture affecting the right arm and leg, mild facial immobility, episodes of profound malaise and lack of energy, inner feelings of tremulousness, excessive unprovoked bouts of perspiration, and accompanying feelings of heat. Abnormalities of movement in the right arm can be seen in video footage of soccer games up to 8 years before his disability came to medical attention. Many of his premorbid personality traits are characteristic of those believed to be associated with the subsequent development of the malady. At least in some patients with Parkinson's disease, the search for instigating aetiological factors should focus 10-20 years before the cardinal signs can be recognised with certainty.     

Clozapine withdrawal symptoms in a Parkinson's disease patient.

Abrupt clozapine withdrawal can cause rebound psychosis and severe somatic symptoms in psychiatric patients. We report on the case of an advanced Parkinson's disease patient who developed myoclonus, tremor, rigidity, hyperreflexia, and stupor after abrupt clozapine withdrawal. The patient's symptoms resolved with treatment with cyproheptadine. This clinical picture suggests serotonergic rebound as an explanation for the patient's symptoms, although other pharmacological mechanisms are possible. Clozapine should be gradually withdrawn over a period of 1 to 2 weeks when possible, and abruptly discontinued only when necessary.     

Omohyoid muscle syndrome in a patient with Parkinson's disease

A 49-year-old man noticed a resting tremor in his right hand and was diagnosed with Parkinson's disease (PD) at the age of 43. Soon thereafter, he noticed a right neck mass that only appeared when he swallowed and was accompanied by an uncomfortable sensation. At the age of 49, he was admitted to our hospital to adjust his medication for PD and to examine the neck mass. The subcutaneous mass was round, soft, and approximately 3 cm in diameter. The symptoms in his neck showed no progression. Resting tremors and rigidity due to his PD were predominantly observed on his right side, but his postural reflex was intact. Cervical echogram revealed that the mass was the belly of the OM itself. Thus, the patient was diagnosed with omohyoid muscle syndrome (OMS). It can be surmised that some susceptibility of the OM itself and/or structural fragility in the surrounding tissues would be involved in the pathogenesis of OMS. In this case, considering that OMS occurred soon after symptoms of PD appeared, we speculated that muscle tone abnormalities due to PD played a role in the development of OMS.     

An integrated approach to patient management in Parkinson's disease.

New concepts about the pathogenesis and pathophysiology of Parkinson's disease have emerged. For these concepts to be useful, they must be understood, and for them to be applied, the psychology of the patient and the patient's family must be understood. The initial consultation is crucial in establishing a successful relationship between a patient, family, and physician. This consultation is analyzed and ways of avoiding errors and misconceptions delineated. Emphasis is placed on imaginitive questioning using the format of the ADL portion of the UPDRS in establishing the diagnosis and following treatment. The rational for starting treatment with selegiline at this time is discussed in the context of the role that increased MAO-B activity plays in the progression of Parkinson's disease. After making the diagnosis and starting treatment with selegiline, deciding when to start levodopa is the next crucial decision. Often as important as deciding when to start levodopa is overcoming the resistance of the patient to accept this treatment. The next crucial decision occurs after the patient develops response fluctuations on levodopa. A format for assessing the fluctuations is presented, and the merits of different treatments, including selegiline, dopamine agonists (bromocriptine and pergolide), and sustained-release or controlled-release levodopa preparations (Sinemet CR), discussed. The management of patients with depression, sleep problems, and advanced disease including postural instability and mental changes are reviewed.     

Speech and gait in Parkinson's disease: When rhythm matters

IntroductionSpeech disturbances in Parkinson's disease (PD) are heterogeneous, ranging from hypokinetic to hyperkinetic types. Repetitive speech disorder has been demonstrated in more advanced disease stages and has been considered the speech equivalent of freezing of gait (FOG). We aimed to verify a possible relationship between speech and FOG in patients with PD.MethodsForty-three consecutive PD patients and 20 healthy control subjects underwent standardized speech evaluation using the Italian version of the Dysarthria Profile (DP), for its motor component, and subsets of the Battery for the Analysis of the Aphasic Deficit (BADA), for its procedural component. DP is a scale composed of 7 sub-sections assessing different features of speech; the rate/prosody section of DP includes items investigating the presence of repetitive speech disorder. Severity of FOG was evaluated with the new freezing of gait questionnaire (NFGQ).ResultsPD patients performed worse at DP and BADA compared to healthy controls; patients with FOG or with Hoehn-Yahr >2 reported lower scores in the articulation, intellibility, rate/prosody sections of DP and in the semantic verbal fluency test. Logistic regression analysis showed that only age and rate/prosody scores were significantly associated to FOG in PD. Multiple regression analysis showed that only the severity of FOG was associated to rate/prosody score.ConclusionsOur data demonstrate that repetitive speech disorder is related to FOG and is associated to advanced disease stages and independent of disease duration. Speech dysfluency represents a disorder of motor speech control, possibly sharing pathophysiological mechanisms with FOG.     

Reversible antecollis associated with pramipexole in a patient with Parkinson's disease

Antecollis is a frequent complication in multiple system atrophy but is rare in Parkinson's disease (PD). We report an 80-year-old patient with a four-year history of PD who developed antecollis six weeks after taking pramipexole (1 mg/day). When assessed in the outpatient clinic, she had antecollis, cogwheel rigidity on the right side, and mild bradykinesia. We found no evidence of myopathic or neurogenic changes in the neck muscles on needle electromyography. We withdrew the pramipexole immediately, and, one week later, her antecollis improved dramatically. This report emphasizes the importance of considering dopamine agonists as a possible cause of antecollis and shows that immediate withdrawal of these drugs may reverse the symptoms.     

Postmortem analysis of adrenal-medulla-to-caudate autograft in a patient with Parkinson's disease

A 53-year-old physician who had a 10-year history of progressive idiopathic parkinsonism survived for 4 months after an autologous adrenal-medulla-to-right-caudate autograft but he received little clinical benefit. A small number of chromaffin cells in the graft site survived; they expressed neurofilament proteins and chromogranin A, but scant tyrosine hydroxylase. The striatum on both sides showed almost complete loss of [3H]mazindol binding to dopamine-uptake sites; the density of dopamine receptors was decreased adjacent to the transplant but increased rostral to the transplant. These results demonstrate that autografted chromaffin cells can survive for 4 months after transplantation and that related changes in dopamine receptors can be quantified.