Influence of dopamine deficiency in early Parkinson's disease on the slow stimulation multifocal-ERG.

PURPOSE: In animal studies intravitreal injection of tetrodotoxin (TTX) results in mfERG waveform changes similar to those observed in glaucoma. As TTX blocks amacrine as well as ganglion cells, there is still a question regarding the underlying cell population responsible for these changes in waveform. In an attempt to assess the contribution of the amacrine cells to these changes, a mfERG was obtained from patients with Parkinson's disease as some amacrine cells are mediated by dopamine, a substance lacking in Parkinson's. METHODS: Eight patients with early Parkinson's disease underwent ophthalmologic examination, testing of contrast sensitivity and electrophysiological examination according to ISCEV standard at least 12 h following their last medication with Dopamine. A slow stimulation mfERG was obtained with a stimulus base interval of 53.3 ms and with a stimulus base interval of 106.6 ms. During MF-ERG recordings 103 hexagons stimulated the central 50 deg of the retina simultaneously and independently (m-sequence 2(13), L(max): 200 cd/m(2), approximately 100% contrast). RESULTS: Contrast sensitivity and ISCEV standard electrophysiological testing was unremarkable. When the mfERG was analyzed, only four patients had an adequate signal-to-noise ratio to allow further data analysis - one of whom was diagnosed with a multi system atrophy in retrospect. The first order response component was analyzed at a filter setting of 10-300 Hz and at 100-300 Hz (OPs) and compared to mfERGs of a control group. On average, in patients, the amplitude of N1P1 was slightly lower in the central and nasal response averages. When the three OPs at a latency of 72-89 ms were analyzed in the 53.3 ms base interval recording, the most marked difference in amplitude was observed in the superior nasal response average of the first OP. Here a mean amplitude of 1.3 nV/deg(2) in patients compared to a mean amplitude of 1.9 nV/deg(2) in the control group (P: 0.08). DISCUSSION: In contrast to our previous findings in NTG, there was a consistent presence of three OPs. Under the stimulus conditions applied, we did not find an influence of dopaminergic amacrine cells on the mfERG in our patients with moderate stages of Parkinsion's. The difficulties in obtaining an adequate signal-to noise ratio due to e.g. muscle artifacts even in Parkinson patients of moderate disease stages render a success of mfERG recording in patients with more advanced stages unlikely. The question of the influence of dopaminergic amacrine cells on the mfERG could possibly be addressed using MPDT in animal research.

Orthostatic tremor during modification of standing.

Primary orthostatic tremor (OT) occurs only during standing. We studied whether modification of the condition standing influences OT. In seven patients with OT, surface EMG was recorded from both tibialis anterior and gastrocnemius muscles during two maneuvers: relief, whereby the patient was gradually lifted by a crane, and tilting, whereby the patient was tilted by a tilting table to positions of 90 degrees (upright standing), 45 degrees (diagonal position), and 0 degrees (lying position). We determined the parameters tremor frequency, tremor intensity, coherence, and phase shift between the different muscles. Relief did not influence OT. In contrast, tilting modified significantly tremor intensity and phase shifts; tremor frequencies and coherences were not influenced. We chose both these maneuvers because of their different impact on the standing condition: relief modifies the factors afferent input and muscle forcing but not the factor postural set, whereas tilting modifies all three factors. The fact that tilting modifies OT, whereas relief does not, suggests an important role of postural set in OT generation. Afferent input and muscle forcing seem to play less important role.

Peroperative transcranial sonography for electrode placement into the targeted subthalamic nucleus of patients with Parkinson disease: technical note.

BACKGROUND: In the search for a better preoperative knowledge of the position of probes and electrodes, we assessed the feasibility and the usefulness of transcranial sonography during surgery for the implantation of stimulation electrodes into the subthalamic nucleus (STN) of patients with Parkinson's disease. METHODS: Transcranial sonography was carried out during stereotactic surgery in 8 patients with Parkinson's disease who had a suitable temporal bone window on the side receiving the electrode. Test stimulation parameters were 130 Hz, 0.1 ms, up to 0 to 4.5 V. RESULTS: The test probe with a diameter of 0.8 mm was visualized through the temporal preauricular window. The correct anatomic position of the electrode tip could be indirectly assessed thanks to the topographic relationship of the STN with the hyperechogenic substantia nigra and the nucleus ruber. The tip position of the final electrode was easily documented. A laterality of 10.5 to 11.5 mm, verified by teleradiographic ventriculography and plain films, was correlated with the best response of symptoms of Parkinson's disease to electrical impulses delivered to the STN. CONCLUSIONS: Transcranial sonography is easily feasible during stereotactic surgery. In combination with the clinical effects of electrostimulation on the symptoms of Parkinson's disease and with stereotactic x-ray images, it enables the assessment and the documentation of the correct position of implanted STN electrodes in real time.

FP-CIT and MIBG scintigraphy in early Parkinson's disease.

Methods provided by nuclear medicine may be helpful in diagnosis of Parkinson's disease (PD). For that purpose, the sensitivity of iodine-123 metaiodobenzylguanidine ([123I]MIBG) scintigraphy and [123I]FP-CIT single photon emission computed tomography (SPECT) was studied in patients with PD onset (Hoehn and Yahr Stage 1). Cerebral [123I]FP-CIT and cardiac [123I]MIBG scintigraphy were carried out in 18 patients with idiopathic Parkinson's disease, according to Hoehn and Yahr Stage 1. For quantification purposes, we calculated the striatum/posterior lobe binding of FP-CIT and the heart-to-mediastinum (H/M) count ratio regarding MIBG scintigraphy. In 15 of 18 patients, we observed markedly reduced or asymmetric striatal FP-CIT tracer accumulation. FP-CIT binding of the affected striatum was significantly lower as compared with that of the unaffected side. Striatal FP-CIT binding correlated significantly with the motor part of the Unified Parkinson's disease rating scale (UPDRS) but not with age, disease duration, or gender. MIBG scintigraphy delivered significant pathological results in 13 of 18 patients. There was no significant correlation between the H/M ratio relating to MIBG scintigraphy and the motor part of UPDRS, age, disease duration, or gender; however, binding of striatal FP-CIT correlated significantly with cardiac MIBG accumulation. According to the clinical criteria, it might be difficult to prove the diagnosis of PD in patients with slight symptoms and in these cases, FP-CIT SPECT and MIBG scintigraphy may contribute to the early diagnosis of PD. In addition, the functional loss of nigrostriatal and cardiac sympathetic neurons seems to be coupled closely.

Improvement of upper limb ataxia and intention tremor allowing cessation of thalamic electrostimulation after four years.

A 34-year-old female patient suffering from multiple sclerosis was treated with thalamic electrostimulation for right dominant brachial ataxia and intention tremor. At the end of the fourth year, the energy of the battery of the impulse generator was depleted. However, the patient was able to use her hands without major impairment with the stimulator OFF; due to a stable reduction of the degree of ataxia and intention tremor. The opposite thalamus received an electrode that was never activated because of a permanent thalamotomy effect. Thus, it can be concluded that restoration of function by means of deep brain stimulation might have been beneficial towards achieving a reorganization and stabilization of subcortico-cortical and cerebellar circuitry, supporting the process of self-repair in this patient with a less aggressive course of multiple sclerosis. However, scientific proof has yet to be found. This exceptional observation emphasizes the need for longterm studies.

Transient dystonia following magnetic resonance imaging in a patient with deep brain stimulation electrodes for the treatment of Parkinson disease. Case report.

Data from previous studies have shown that magnetic resonance (MR) imaging of the head can be performed safely in patients with deep brain stimulators. The authors report on a 73-year-old patient with bilaterally implanted deep brain electrodes for the treatment of Parkinson disease, who exhibited dystonic and partially ballistic movements of the left leg immediately after an MR imaging session. Such dystonic or ballistic movements had not been previously observed in this patient. In the following months, this focal movement disorder resolved completely. This case demonstrates the possible risks of MR imaging in patients with deep brain stimulators.

[Effect of deep brain stimulation on glottal phonation in patients with Parkinson's disease and multiple sclerosis]. / Auswirkungen der Elektrostimulation subkortikaler Hirnstrukturen auf das glottale Schwingungsverhalten bei Patienten mit Morbus Parkinson und multipler Sklerose.

The present study examines the effect of neurostimulatory operations on glottal phonation of 3 parkinsonian patients and 3 patients with multiple sclerosis. With the help of two voice analysis programs (MDVP from Kay Elemetrics and EEG Program by Marasek) for the acoustic and electroglottographic definition of voice characteristics, vowel productions of the patients, which were recorded under two conditions (with and without stimulation), were analysed. In a first step, significantly different intrasubject means in the two conditions indicate the effect of neurostimulation. The strength of the effect differs among subjects, particularly in the case of patients with Parkinson's disease. In a second step, a gender-differentiated comparison of the individual patient's data (recorded with and without stimulation) with a group of normal voice speakers (150 male and 150 female speakers) is carried out. This intersubject comparison proves useful in that it relativizes the results from the intrasubject comparison. It is shown for the parkinsonian patients that stimulation causes a relative deterioration of the glottal cycle, while for the patients with multiple sclerosis a tendency for hyperfunctional phonation is observed. In the latter case, the results suggest the need for long-term monitoring of phonation behaviour during chronic electrical stimulation.

Influence of proprioceptive input on parkinsonian tremor.

Previous studies have shown a modification of parkinsonian tremor (PT) by proprioceptive input induced by passive joint movements. The authors investigated the impact of electrically evoked proprioceptive input on PT. In eight patients with PT they recorded surface EMG from the opponens pollicis muscle, and forearm extensors and flexors. Rhythmic electrical stimulation was applied to the ipsilateral median nerve at the wrist using a submaximal stimulus intensity and stimulus frequencies between two stimuli per second and five stimuli per second. The tremor frequency did not adapt to the stimulus frequency. Tremor frequency of parkinsonian resting tremor increased significantly in the directly stimulated opponens pollicis muscle (mean +/- standard deviation, 4.35 +/- 0.64 Hz without stimulation versus 4.53 +/- 0.68 Hz with stimulation; P < 0.05, paired t-test), the not directly stimulated forearm muscles (4.90 +/- 0.72 Hz versus 5.18 +/- 0.73 Hz, P < 0.001), and the upper arm muscles (5.13 +/- 0.61 Hz versus 5.36 +/- 0.68 Hz, P < 0.01). Furthermore, the parkinsonian postural tremor accelerated significantly during ipsilateral median nerve stimulation (5.31 +/- 0.99 Hz versus 5.44 +/- 1.03 Hz, P < 0.05). Parkinsonian resting tremor in the forearm muscles also accelerated significantly during ipsilateral ulnar nerve stimulation (4.85 +/- 0.57 Hz versus 5.05 +/- 0.65 Hz, P < 0.05). Contralateral median nerve stimulation had no significant effect. These results suggest a close interaction between proprioceptive input and PT generation.