Interpretation of clinical trials comparing different drug regimens for Parkinson's disease (PD) is complicated by the different dose intensities used: higher doses of levodopa and, possibly, other drugs produce better symptomatic control but more late complications. To address this problem, conversion factors have been calculated for antiparkinsonian drugs that yield a total daily levodopa equivalent dose (LED). LED estimates vary, so we undertook a systematic review of studies reporting LEDs to provide standardized formulae. Electronic database and hand searching of references identified 56 primary reports of LED estimates. Data were extracted and the mean and modal LEDs calculated. This yielded a standardized LED for each drug, providing a useful tool to express dose intensity of different antiparkinsonian drug regimens on a single scale. Using these conversion formulae to report LEDs would improve the consistency of reporting and assist the interpretation of clinical trials comparing different PD medications.

Systematic review of levodopa dose equivalency reporting in Parkinson's disease

A set of related medical disorders that lack a proper classification system and diagnostic criteria is like a society without laws. The result is incoherence at best, chaos at worst. For this reason, the International Classification of Headache Disorders (ICHD) is arguably the single most important breakthrough in headache medicine over the last 50 years. The ICHD identifies and categorizes more than a hundred different kinds of headache in a logical, hierarchal system. Even more important, it has provided explicit diagnostic criteria for all of the headache disorders listed. The ICHD quickly became universally accepted, and criticism of the classification has been minor relative to that directed at other disease classification systems. Over the 20 years following publication of the first edition of the ICHD, headache research has rapidly accelerated despite sparse allocation of resources to that effort. In summary, the ICHD has attained widespread acceptance at the international level and has substantially facilitated both clinical research and clinical care in the field of headache medicine.

International Classification of Headache Disorders

/pdf/inflammation-as-a-central-mechanism-in-alzheimer-s-disease-eiiqrx1far.pdf

Inflammation as a central mechanism in Alzheimer's disease

Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins in the healthy and diseased brain. As a result, there is a large body of evidence that associates BDNF with neuronal maintenance, neuronal survival, plasticity, and neurotransmitter regulation. Patients with psychiatric and neurodegenerative disorders often have reduced BDNF concentrations in their blood and brain. A current hypothesis suggests that these abnormal BDNF levels might be due to the chronic inflammatory state of the brain in certain disorders, as neuroinflammation is known to affect several BDNF-related signaling pathways. Activation of glia cells can induce an increase in the levels of pro- and antiinflammatory cytokines and reactive oxygen species, which can lead to the modulation of neuronal function and neurotoxicity observed in several brain pathologies. Understanding how neuroinflammation is involved in disorders of the brain, especially in the disease onset and progression, can be crucial for the development of new strategies of treatment. Despite the increasing evidence for the involvement of BDNF and neuroinflammation in brain disorders, there is scarce evidence that addresses the interaction between the neurotrophin and neuroinflammation in psychiatric and neurodegenerative diseases. This review focuses on the effect of acute and chronic inflammation on BDNF levels in the most common psychiatric and neurodegenerative disorders and aims to shed some light on the possible biological mechanisms that may influence this effect. In addition, this review will address the effect of behavior and pharmacological interventions on BDNF levels in these disorders.

/pdf/brain-derived-neurotrophic-factor-in-brain-disorders-focus-5311blpues.pdf

Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation

The state of the intestinal environment can have profound effects on the activity of the central nervous system through the physiological contributions of the microbiota, regulation of intestinal barrier function, and altered activity of peripheral neurons. The common language employed for much of the gut-brain communication is the modulation of immune activity. Chronic proinflammatory immune activity is increasingly being recognized as a fundamental element of neurodegenerative disorders, and in Parkinson’s disease, inflammation in the intestine appears particularly relevant in pathogenesis. We review the evidence that intestinal dysfunction is present in Parkinson’s disease and that it may reflect the earliest manifestations of Parkinson’s disease pathology, and we link these findings to dysregulated immune activity. Based on this, we present a model for Parkinson’s disease pathogenesis in which the disorder originates in the intestine and progresses with inflammation as its underlying mechanism. More in-depth investigations into the physiological mechanisms underlying peripheral pre-motor symptoms in Parkinson’s disease are expected to lead to the development of novel diagnostic and therapeutic measures that can slow or limit progression of the disease to more advanced stages involving debilitating motor and cognitive symptoms.

/pdf/the-gut-brain-axis-is-intestinal-inflammation-a-silent-4d59ox3reh.pdf

The gut-brain axis: is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis?

The interleukin 1 alpha, interleukin 1 beta, interleukin 6 and alpha-2-macroglobulin serum levels in patients with early or late onset Alzheimer's disease, mild cognitive impairment or Parkinson's disease

Broad bean (Vicia faba)--a natural source of L-dopa--prolongs "on" periods in patients with Parkinson's disease who have "on-off" fluctuations

We investigated the type and frequency of interictal primary headache and peri-ictal headache in 109 patients with partial-onset and 26 patients with generalized onset seizures in this study. Interictal headaches were present in 50 (40.7%) of 135 patients. Comparing the interictal headache on the basis of seizure type, we couldn't find any significant difference between the seizure groups. Seventy-nine (58.51%) patients had peri-ictal headache. Eleven of these patients had pre-ictal headache (PriH), three of all had ictal headache and, 56 of these had post-ictal headache (PoiH). PriH and PoiH were more frequently encountered before and after secondary generalized tonic-clonic seizures (GTCS) compared to other seizure groups. The type of pain in PoiH was 'throbbing' in complex partial seizures and 'steady' in GTCS.

Seizure-related headache in patients with epilepsy.

Patients admitted to movement disorders outpatient unit at a university hospital between January 2002 and June 2007 were screened for psychogenic movement disorders (PMDs). Out of 1,743 patients, 49 patients (2.8%), including four children, were diagnosed to have PMDs. Women to men ratio was 34/15. The mean age and the age-at-onset were 41 +/- 17 years and 36 +/- 15 years in the adult group, and 10 +/- 2 and 9 +/- 2 years in children. Among the whole group, 44% had tremor, 24% dystonia, 12% pure gait disorders, 8% parkinsonism, 6% chorea-ballism, and 4% tic disorder. PMD developed acutely in 85% of patients, and distractibility was observed in 83%. Of the patients, 81% met the criteria for clinically established PMD, whereas 16% for documented and 2% for probable PMD. Although our data was obtained from a different culture, our results showed that hospital-based frequency and phenomenological features between our PMD group and previously reported ones are similar.

/pdf/clinical-characteristics-of-49-patients-with-psychogenic-bw6lcx2ji0.pdf

Clinical characteristics of 49 patients with psychogenic movement disorders in a tertiary clinic in Turkey.

Psychotic symptoms (PS) in Parkinson's disease (PD) usually develop as a side effect of the dopaminergic therapy and consist of hallucinations and delusions. We observed that PD patients who developed delusions tend to be younger than those with hallucinations and we aimed to investigate the validity of this observation. The medical records of 127 PD patients with PS were reviewed and 76 patients who were on treatment with dopamine agonists with or without levodopa at the time of developing PS were included. Patients were stratified into 3 groups according to the subtypes of PS: patients with solely hallucinations (n = 46), solely delusions (n = 18), and both types (n = 12). The groups were compared with respect to the age-at-onset of PD and PS, duration of PD, Activities of Daily Living (ADL) and motor subscale scores of Unified PD Rating Scale (UPDRS), and levodopa equivalent dose of the dopaminergic agents administered at the time of PS onset. The mean age-atonset of PD and PS was significantly younger (p = 0.0001) in patients with delusions (49 and 55.9 years) than those with hallucinations (61.9 and 68.9 years). The same parameters were also significantly different (p = 0.002 and p = 0.001, respectively) between the groups of patients with concurrent delusions and hallucinations (51.7 and 57.2 years) and those with only hallucinations. ADL and motor subscale scores were higher in patients with hallucinations (p = 0.016 and p = 0.013) compared with those noted in patients with delusions despite similar disease duration. The mean levodopa equivalent doses of the dopaminergic agents administered at the time of onset of PS did not differ between the groups. This study supported an association of delusions with younger onset of both PD and psychosis as compared with hallucinations. However, additional factors related to this association remain to be elucidated.

Sibel Ertan

Papers

The interleukin 1 alpha, interleukin 1 beta, interleukin 6 and alpha-2-macroglobulin serum levels in patients with early or late onset Alzheimer's disease, mild cognitive impairment or Parkinson's disease

Broad bean (Vicia faba)--a natural source of L-dopa--prolongs "on" periods in patients with Parkinson's disease who have "on-off" fluctuations

Seizure-related headache in patients with epilepsy.

Clinical characteristics of 49 patients with psychogenic movement disorders in a tertiary clinic in Turkey.

Relationship between age and subtypes of psychotic symptoms in Parkinson's disease.