Medulla In Patients Research Articles

BDNF is altered in a brain-region specific manner and rescues deficits in Spinocerebellar Ataxia Type 1

Spinocerebellar ataxia type 1 (SCA1) is an adult-onset, dominantly inherited neurodegenerative disease caused by the expanded polyQ tract in the protein ATAXIN1 (ATXN1) and characterized by progressive motor and cognitive impairments. There are no disease-modifying treatments or cures for SCA1. Brain-derived neurotrophic factor (BDNF) plays important role in cerebellar physiology and has shown therapeutic potential for cerebellar pathology in the transgenic mouse model of SCA1, ATXN1[82Q] line that overexpress mutant ATXN1 under a cerebellar Purkinje-cell-specific promoter. Here we demonstrate decreased expression of brain derived neurotrophic factor (BDNF) in the cerebellum and medulla of patients with SCA1. Early stages of disease seem most amenable to therapy. Thus, we next quantified Bdnf expression in Atxn1154Q/2Q mice, a knock-in mouse model of SCA1, during the early symptomatic disease stage in four clinically relevant brain regions: cerebellum, medulla, hippocampus and motor cortex. We found that during the early stages of disease, Bdnf mRNA expression is reduced in the hippocampus and cerebellum, while it is increased in the cortex and brainstem. Importantly, we observed that pharmacological delivery of recombinant BDNF improved motor and cognitive performance, and mitigated pathology in the cerebellum and hippocampus of Atxn1154Q/2Q mice. Our findings demonstrate brain-region specific deficiency of BDNF in SCA1 and show that reversal of low BDNF levels offers the potential for meaningful treatment of motor and cognitive deficits in SCA1.

PSAT013 Elevated Plasma Free Metanephrines with No Evidence of Pheochromocytoma in a Patient with Multiple Endocrine Neoplasia Type 2A

Abstract Background Adrenal medullary hyperplasia (AMH) is arbitrarily defined by adrenal medullary proliferation measuring less than 1 cm while larger lesions are considered pheochromocytoma. Some patients with MEN2 present with adrenal medullary hyperplasia (AMH), which is a precursor of pheochromocytomas. Clinical Case A 22-year-old female with a past medical history of MEN2A. She is positive for germline mutation in RET proto-oncogene at 10q11.2 exon 11, position 634 from cysteine to arginine. She was evaluated for a 1cm left thyroid nodule, which required total thyroidectomy for Medullary Thyroid Cancer. Pathology revealed a 0.5cm deposit on the largest dimension, clear margins, and no angiovascular, or lymphovascular invasion, surgery was complicated by hypoparathyroidism. She complained of intermittent anxiety and fatigue but was otherwise asymptomatic. Physical examination is unremarkable except for thyroidectomy scar and multiple exostoses. On 8/5/2011 plasma-free metanephrines were elevated at 83 pg/ml (<57pg/ml) and Free normetanephrine was 45 pg/ml (<145pg/ml). Over the next years, her plasma-free metanephrine levels have been checked approximately every 6 months ranging between 63-106pg/ml with free plasma normetanephrine in normal ranges (30-81pg/ml). However, on 2/2021, her plasma normetanephrine level increased to 304pg/ml. More recently, on 11/30/2021 her free normetanephrine levels reached 671pg/ml and free Metanephrine 131pg/ml. She had two MRIs of the abdomen and pelvis over the years and both showed unremarkable adrenal glands. NM I-123 MIBG scintigraphy reported physiologic symmetric activity in the adrenal glands. Finally, she had GA-68 DOTATATE PET/CT with no suspicious radiotracer avid lesion in the abdominopelvic organs. Given the persistent elevation on plasma metanephrines, we decided to start the patient on Doxazosin prophylactically while we continue biochemical and imaging surveillance. Conclusion Our patient has a persistent elevation in plasma-free metanephrines with no evidence of pheochromocytoma in abdominal imaging. The earliest abnormality in the adrenal medulla in patients with MEN 2 is diffuse hyperplasia with a reduction in the cortical/medullary ratio (1). This hyperplasia is considered to be a precursor of pheochromocytoma in patients with MEN 2 and in our case the most likely explanation for the progressive elevation in plasma-free metanephrines (1). There is a strong molecular relationship between AMH and Pheochromocytoma (2), close monitoring for progression to pheochromocytoma is necessary for all patients with AMH. The presence of markedly elevated plasma metanephrines in an asymptomatic patient with no evidence of pheochromocytoma poses a therapeutic dilemma for preemptive use of alpha blockade and the potential need for a medical alert bracelet. References (1) Cho, K et al "Adrenal Medullary disease in Multiple Endocrine Neoplasia II". AJR 134: 23-29. (2) Korpershoek, E et al "Adrenal Medullary Hyperplasia Is a Precursor Lesion for Pheochromocytoma in MEN2 Syndrome". Neoplasia. 2014 Oct; 16(10): 868–873 Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Amide proton transfer magnetic resonance imaging to evaluate renal impairment in patients with chronic kidney disease

ObjectiveWe aimed to investigate the value of amide proton transfer magnetic resonance imaging (APT-MRI) in the classification of chronic kidney disease (CKD). Materials and methodsA total of 30 patients with chronic kidney disease (CKD) and 25 healthy volunteers were enrolled in this study. Patients with chronic kidney disease were divided into two groups according to glomerular filtration rates: mild and moderate-to-severe renal impairment. Differences in cortical and medullary APT values were compared, and the correlation between corticomedullary APT values and glomerular filtration rates was analyzed. Data were statistically analyzed using SPSS 23.0. ResultsBased on glomerular filtration rates, 14 patients were assigned to the mild renal impairment group, and 16 were assigned to the moderate-to-severe renal impairment group. Both of the cortical and medullary APT values showed a gradually increasing trend in the control, the mild, and the moderate-to-severe renal impairment groups. Cortical APT values were higher than medullary APT values in all the control and renal impairment groups (P < 0.05). APT values of the right renal cortex (r = −0.80, P < 0.05) and medulla (r = −0.83, P < 0.05) were negatively correlated with the glomerular filtration rate. Results of the receiver operating characteristic (ROC) curve analysis showed that corticomedullary APT values had high diagnostic efficacy in assessing different degrees of renal impairment. ConclusionsThe APT values of the cortex and medulla in patients with CKD gradually increased with disease progression. These findings indicated that APT imaging can be used to evaluate renal function and renal injury in patients with CKD.

3D-Visualization of Neurovascular Compression at the Ventrolateral Medulla in Patients with Arterial Hypertension

PurposeControversy exists on the association of arterial hypertension (HTN) and neurovascular compression (NVC) at the ventrolateral medulla (VLM). No standardized and reproducible technique has been introduced yet for detection of NVC in HTN. This study aimed to generate, analyze and compare different results of exact reproducible anatomical 3D-representations of the VLM in patients with HTN, based on magnetic resonance imaging (MRI).MethodsA 3T scanner provided MRI (T2-constructive interference in steady state (CISS) high resolution imaging and three-dimensional Time-of-flight (3D-TOF) angiography) from the posterior fossa of 44 patients with clinical treatment-resistant HTN. Image processing consists of segmentation of the CISS data, registration and fusion of the CISS and TOF data and visualization. For each patient two 3D-visualizations (before and after fusion) were obtained. The reproduction quality of the vessels, flow-related signal variability and pulsation artifacts were analyzed and compared, using a ranking score.ResultsIntegrating vascular information from TOF into CISS data reduced artifacts in 3D-visualizations of exclusively processed CISS data. The quality of 3D-visualization of the vessels near the brain stem was significantly improved (p = 0.004). The results were reproducible and reliable. The quality of the 3D-presentations of neurovascular relationships at the VLM improved significantly (p < 0.001).ConclusionThe 3D-visualization of fused image data provides an excellent overview of the relationship between cranial nerves and vessels at the VLM and simplifies the detection of NVC in HTN. It provides a powerful tool for future clinical and scientific research. Although microvascular decompression (MVD) in treatment resistant HTN is not a standard procedure, it can be discussed in selected patients with intractable severe HTN.

Клиническое значение КТ-перфузии у пациентов с камнями мочеточника

Urinary stone disease is one of the most significant urologic diseases, since its prevalence increases annually, which makes it necessary to study and improve effective preventive measures, diagnostic methods and to implement new treatment interventions. to study changes in blood flow in the renal cortex and medulla in patients with ureteral stones using CT perfusion. From 2017 to 2019, a total of 53 patients with upper ureteric stones were evaluated at the Russian-Japanese Center for Imaging and the Institute of Urology and Reproductive Health of the FGAOU VO I.M. Sechenov First Moscow State Medical University. Preoperatively, all patients underwent CT perfusion. The study was performed on a Toshiba Aquilion One 640 in volume mode with a slice thickness of 0.5 mm. In this study, blood flow changes were evaluated depending on the degree of dilatation of collecting system. In patients without dilatation of the collecting system, the average values of cortical and medullary blood flow and blood volume were within normal values. In patients with a dilatation of collecting system, there were significant differences cortical and medullary blood flow between the affected renal unit and contralateral side (27% and 34%, respectively). A decrease in cortical and medullar perfusion by 55% and 58%, respectively, in patients with the dilatation of calyxes was more pronounced in comparison with a decrease in perfusion in patients with the dilatation of only the ureter and pelvis. CT perfusion performed on the 640-slice CT scan allows an objective assessment of changes in renal blood flow in patients with ureteric stones.

Diffusional kurtosis imaging of kidneys in patients with hyperuricemia: initial study.

At present, there remains a lack of a reliable indicator for monitoring renal function in patients with hyperuricemia. This study aimed to evaluate the feasibility of diffusion kurtosis imaging in the assessment of renal function in patients with hyperuricemia. A total of 75 male participants, including 25 with asymptomatic hyperuricemia, 25 with gouty arthritis, and 25 age-matched male healthy controls, were enrolled in this study. Diffusion kurtosis imaging data were acquired to derive axial (Ka), radial (Kr), and mean kurtosis (MK), fractional anisotropy, axial (Da), radial (Dr), and mean diffusivity (MD) for comparisons among the three groups. They were also correlated with estimated glomerular filtration rate (eGFR). The MK values of the renal cortex and medulla and Kr value of the renal medulla in patients with asymptomatic hyperuricemia and gouty arthritis significantly increased compared with those in the controls (P < 0.05). Patients with gouty arthritis showed significant higher cortical and medullary Ka values compared with the other two groups (P < 0.05). The cortical Kr values of the asymptomatic hyperuricemia and gouty arthritis patients were significantly higher than that of the controls (P < 0.05). The medullary fractional anisotropy value showed a significant difference between the control and gouty arthritis groups (P < 0.05). No correlation was found between any diffusion kurtosis imaging parameters and eGFR value. Diffusion kurtosis imaging is feasible in the assessment of the early changes of renal cortex and medulla in patients with hyperuricemia.

Kidney Cancers in Adolescents &amp; Young Adults

Kidney Cancers in Adolescents &amp; Young Adults

Congenital adrenal hyperplasia and the function of adrenal medulla.

The most common form of congenital adrenal hyperplasia (CAH) is the deficiency of steroid 21-hydroxylase which results from deletion or mutation of the cytochrome P450 21-hydroxylase gene. The low level of glucocorticoids and in some cases low level of mineralocorticoids has an important pathophysiological influence on the axis of the hypothalamo-pituitary-adrenal cortex. Using determination of plasmatic metanephrine, normetanephrine and chromogranin A, we wanted to investigate the structure and function of adrenal medulla in patients with CAH, because adrenocortical and adrenomedullary systems are intimately linked anatomically and functionally. Levels of plasmatic metanephrine, normetanephrine and chromogranin A were measured in our group of 37 patients (age range: 5-45years, 18 females and 19 males) with the classic salt-wasting form of CAH. The reference range was 73% for metanephrine (<10ng/L, 83.3% females, 63.2% males) and 59.5% for metanephrine (<15ng/L, 72.2% females, 47.4% males). The concentration of plasmatic nephrines in the first quartile reference range was achieved in the case of metanephrine in all patients (<23ng/L), and in the case of normetanephrine in 86.5% of patients (<42.5ng/L). The level in chromogranin A was normal in all patients. No significant differences were found in plasmatic concentrations of nephrines and chromogranin A between males and females with CAH, nor was there a significant correlation with genetic results (severe or moderate salt-wasting form of CAH). Impaired secretion of glucocorticoids in patients with CAH leads to the structural changes in adrenal medulla which are expressed by low production of metanephrine, and to a lesser extent, normetanephrine.

Hypocalcaemia and a low cardiac output after intravenous codeine phosphate injection: need for an additional mechanism to remove ionized calcium.

A severe degree of hypotension in children followed the intravenous administration of codeine phosphate in several case reports—histamine release was its presumed root cause [1–3]. We also report cardiovascular collapse following accidental bolus intravenous injection of 30 mg (74 μmol) codeine phosphate, but it was associated with a surprising profound degree of hypocalcaemia. A quantitative analysis is provided along with a novel hypothesis to explain the timing and the profound degree of hypocalcaemia that followed the administration of codeine phosphate. We extend this observation to the initiation of kidney stone formation. The conundrum is that while calcium oxalate deposits grow progressively to form Randall's plaque, calcium oxalate does not precipitate in vitro at prevailing concentrations of ionized Ca2+ and oxalate [4]. Since the nidus of the commonest type of kidney stone, calcium oxalate, is hydroxyapatite, it has been postulated that this nidus permits the precipitation of calcium oxalate [5]. However, it is not known how the initial deposit of hydroxyapatite can occur on the basolateral aspect of the ascending thin limb of the loop of Henle in the inner medulla in patients with idiopathic hypocalciuria. We speculate that the first deposit is a precipitate of calcium carbonate (CaCO3).

Focal lesions of the corticospinal tract demonstrated by diffusion tensor imaging in patients with diffuse axonal injury

Diffusion tensor imaging (DTI) with fiber tractography (FT) could be useful for exploration of the state of the corticospinal tract (CST) at the subcortical white matter level. The purpose of this study was to demonstrate focal lesions of the CST in patients with diffuse axonal injury (DAI), using DTI with FT. Two patients with DAI and six normal control subjects were recruited to this study. DTI was performed using 1.5-T with a synergy-L Sensitivity Encoding (SENSE) head coil. Fractional anisotropy (FA) and apparent diffusion coefficients (ADC) were measured using a region of interest (ROI) method. FTs were obtained with FA <0.3 and an angle change >45 degrees as termination criteria. On the DTI with FT, the focal lesions, which could not observed using routine brain MRI, were detected in the left brainstem of patient 1 and in the right pons and the left and right medulla of patient 2. The patients showed significantly decreased FA values in the focal lesions compared to normal controls. DTI with FT demonstrated focal lesions at the brainstem that had not been revealed by conventional brain MRI; these focal lesions explained the weaknesses of the patients. We conclude that DTI with FT may be a useful modality for use in investigating the status of CST in patients with DAI.

Functional Evaluation of Transplanted Kidneys with Diffusion-weighted and BOLD MR Imaging: Initial Experience

To prospectively evaluate feasibility and reproducibility of diffusion-weighted (DW) and blood oxygenation level-dependent (BOLD) magnetic resonance (MR) imaging in patients with renal allografts, as compared with these features in healthy volunteers with native kidneys. The local ethics committee approved the study protocol; patients provided written informed consent. Fifteen patients with a renal allograft and in stable condition (nine men, six women; age range, 20-67 years) and 15 age- and sex-matched healthy volunteers underwent DW and BOLD MR imaging. Seven patients with renal allografts were examined twice to assess reproducibility of results. DW MR imaging yielded a total apparent diffusion coefficient including diffusion and microperfusion (ADC(tot)), as well as an ADC reflecting predominantly pure diffusion (ADC(D)) and the perfusion fraction. R2* of BOLD MR imaging enabled the estimation of renal oxygenation. Statistical analysis was performed, and analysis of variance was used for repeated measurements. Coefficients of variation between and within subjects were calculated to assess reproducibility. In patients, ADC(tot), ADC(D), and perfusion fraction were similar in the cortex and medulla. In volunteers, values in the medulla were similar to those in the cortex and medulla of patients; however, values in the cortex were higher than those in the medulla (P < .05). Medullary R2* was higher than cortical R2* in patients (12.9 sec(-1) +/- 2.1 [standard deviation] vs 11.0 sec(-1) +/- 0.6, P < .007) and volunteers (15.3 sec(-1) +/- 1.1 vs 11.5 sec(-1) +/- 0.5, P < .0001). However, medullary R2* was lower in patients than in volunteers (P < .004). Increased medullary R2* was paralleled by decreased diffusion in patients with allografts. A low coefficient of variation in the cortex and medulla within subjects was obtained for ADC(tot), ADC(D), and R2* (<5.2%), while coefficient of variation within subjects was higher for perfusion fraction (medulla, 15.1%; cortex, 8.6%). Diffusion and perfusion indexes correlated significantly with serum creatinine concentrations. DW and BOLD MR imaging are feasible and reproducible in patients with renal allografts.

The 58th Annual Meeting of the American Academy of Neurology San Diego, California April 1-8, 2006

The 58th Annual Meeting of the American Academy of Neurology San Diego, California April 1-8, 2006

The A.J. Ladman AAA/Wiley Exemplary Service Award

The A.J. Ladman AAA/Wiley Exemplary Service Award

Hypertension in patients with neurovascular compression is associated with increased central sympathetic outflow.

Recent data suggest a causal relationship between essential hypertension and neurovascular compression (NVC) at the rostral ventrolateral medulla. An increase of central sympathetic outflow might be an underlying pathomechanism. The sympathetic nerve activity to muscle was recorded in 21 patients with hypertension with NVC (NVC+ group) and in 12 patients with hypertension without NVC (NVC- group). Heart rate variability, respiratory activity, BP, and central venous pressure at rest and during unloading of cardiopulmonary baroreceptors with lower-body negative pressure and during a cold pressor test were also measured. Resting sympathetic nerve activity to muscle was twice as high in the NVC+ group compared with the NVC- group (34 +/- 22 versus 18 +/- 6 bursts/min; P < 0.05). Resting heart rate (P = 0.06) and low- to high-frequency power ratio values (P = NS) (as indicators of cardiac sympathovagal balance) tended to be augmented as well in the NVC+ group. The sympathetic nerve activity to muscle response to the cold pressor test was increased in the NVC+ group versus the NVC- group (+15 +/- 11 versus 6 +/- 12 bursts/min; P = 0.05), but hemodynamic and sympathetic nerve responses to lower-body negative pressure did not differ between the two groups. It is concluded that NVC of the rostral ventrolateral medulla in patients with essential hypertension is accompanied by increased central sympathetic outflow. Therefore, these data support the hypothesis described in the literature: in a subgroup of patients, essential hypertension might be causally related to NVC of the rostral ventrolateral medulla, at least in part, via an increase in central sympathetic outflow.

1H-MRS evidence of neurodegeneration and excess glutamate + glutamine in ALS medulla.

To determine whether short echo-time (TE) proton magnetic resonance spectroscopic imaging (1H-MRSI) can detect in vivo differences in signal intensities of specific metabolites in the medulla of patients with ALS compared with healthy individuals and whether these metabolites could be useful surrogate markers of disease. 1H-MRSI can detect N-acetylaspartate + N-acetylaspartylglutamate (abbreviated NAx), which is localized to neurons, and glutamate (Glu) + glutamine (Gln), abbreviated Glx, which may be important in ALS pathogenesis. The medulla is an ideal region to study ALS because of its high density of nuclei and fiber tracts that frequently undergo degeneration, even when more rostral brain regions show minimal pathology. Ten patients with ALS and seven healthy control subjects underwent short TE 1H-MRSI on a 1.5 T clinical imaging system. Signal intensities of NAx and Glx were normalized to creatine-phosphocreatine and compared between groups. Compared with normal subjects, the medulla of patients with ALS had 17% lower NAx (p = 0.03) and 55% higher Glx (p = 0.02) signals. Bulbar symptoms, represented by the ALS Functional Rating Scale, correlated with Glx (r = -0.68, p = 0.03) but not NAx (r = 0.22, p = 0.53). There is in vivo 1H-MRSI evidence of neuronal degeneration or loss and excess Glu + Gln in the medulla of patients with ALS. Although this cross-sectional study cannot identify which change occurred first, the higher Glx signal in the medulla of patients with more dysarthria and dysphagia is consistent with the hypothesis of Glu excitotoxicity in ALS pathogenesis. Longitudinal 1H-MRSI studies of the medulla (and other brain regions) in more patients with ALS are required to confirm these findings and to determine whether such metabolite changes will be useful in monitoring disease progression, in clinical diagnosis, and in understanding the pathogenesis of ALS.

MR spectroscopy in amyotrophic lateral sclerosis/motor neuron disease

Proton magnetic resonance spectroscopy ( 1H-MRS) and proton magnetic resonance spectroscopic imaging ( 1H-MRSI) have been used to identify neuronal dysfunction and/or loss in vivo in patients with various neurological diseases, including amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). Both long and short echo time (TE) proton spectroscopy reveal the brain metabolites choline (Cho), creatine/phosphocreatine (Cr), and N-acetyl (NA) groups. Because NA groups are localized to mature neurons and Cr is homogeneously distributed throughout the brain, the NA/Cr ratio is considered an index of neuronal integrity. Long TE proton spectroscopic studies have revealed significantly decreased NA/Cr values in the sensorimotor cortex and brainstem of patients with ALS, consistent with neuronal dysfunction and/or loss. The amount of NA/Cr decrease appears to be directly proportional to the degree of clinical upper motor neuron deficit. Short TE 1H-MRS and 1H-MRSI also reveal other metabolites such as glutamate (Glu) and glutamine (Gln), which have been implicated in the ALS/MND disease process. Preliminary results of short TE 1H-MRSI of the medulla in patients with ALS/MND have revealed significantly decreased NA/Cr values and abnormally elevated Glu+Gln/Cr ratios, compared to control individuals. The latter values were higher in patients with more rapid disease. Although it is unclear whether the elevation of Glu+Gln/Cr precedes or follows the neuronal (and axonal) degeneration in the medulla of these patients, its occurrence provides in vivo evidence of abnormal glutamate metabolism in the CNS parenchyma of patients with ALS/MND.

Clinical experience with cotransplantation of peripheral nerve and adrenal medulla in patients with Parkinson's disease

Abstract Coimplants of adrenal medulla (AM) and peripheral nerve (PN) in animal models of Parkinson's disease (PD) have shown that AM cells survive longer, tend to show neuronal phenotype, and enhance sprouting of host fibers. Since 1987, our implants of perfused AM and fetal ventral mesencephalon (FVM) in PD patients have achieved varying degrees of clinical improvement. If the donor tissue determines the improvement, different types of implants should result in qualitatively and quantitatively different degrees of improvement. The purpose of this study is to determine whether or not the clinical course, improvement slope, and reduction of medication observed in PD patients who undergo tissue transplantation (Tx) depend on the donor tissue type. In a pilot study, four grade IV-V PD patients received implants of precoincubated autologous AM and intercostal nerve in the caudate nucleus (open surgery). Clinical assessment was based on international scales (UPD) as reported for Tx of FVM and perfused AM. There were no systemic or neurologic complications. Four years post-Tx, longer On phases and improved PD symptoms (ADL and motor-UPD) in On and Off persist in four cases, with reduced dyskinesias. Progress appears to be step-wise, starting within weeks of Tx (similar to AM and sooner than our FVM implants), followed by a period of stability and, after a second wave of improvement 12–18 months post-Tx (similar to FVM implants), continues to date. L-dopa medication has been reduced by more than 60 % and dopamine agonist use has not resumed. We conclude that our recipients continue to be clinically better than prior to Tx. The course of recovery after co-Tx of AM and PN differs from that of FVM or AM implants. This fact may be related to the etiological factors that produce the improvement.

Clinical experience with cotransplantation of peripheral nerve and adrenal medulla in patients with Parkinson's disease.

Coimplants of adrenal medulla (AM) and peripheral nerve (PN) in animal models of Parkinson's disease (PD) have shown that AM cells survive longer, tend to show neuronal phenotype, and enhance sprouting of host fibers. Since 1987, our implants of perfused AM and fetal ventral mesencephalon (FVM) in PD patients have achieved varying degrees of clinical improvement. If the donor tissue determines the improvement, different types of implants should result in qualitatively and quantitatively different degrees of improvement. The purpose of this study is to determine whether or not the clinical course, improvement slope, and reduction of medication observed in PD patients who undergo tissue transplantation (Tx) depend on the donor tissue type. In a pilot study, four grade IV-V PD patients received implants of precoincubated autologous AM and intercostal nerve in the caudate nucleus (open surgery). Clinical assessment was based on international scales (UPD) as reported for Tx of FVM and perfused AM. There were no systemic or neurologic complications. Four years post-Tx, longer On phases and improved PD symptoms (ADL and motor-UPD) in On and Off persist in four cases, with reduced dyskinesias. Progress appears to be stepwise, starting within weeks of Tx (similar to AM and sooner than our FVM implants), followed by a period of stability and, after a second wave of improvement 12-18 months post-Tx (similar to FVM implants), continues to date. L-dopa medication has been reduced by more than 60% and dopamine agonist use has not resumed. We conclude that our recipients continue to be clinically better than prior to Tx. The course of recovery after co-Tx of AM and PN differs from that of FVM or AM implants. This fact may be related to the etiological factors that produce the improvement.

Increased glucose metabolism in the medulla of patients with palatal myoclonus

Hypertrophic degeneration of the inferior olivary nuclei is the pathologic substrate for palatal myoclonus, but the physiologic correlate of this finding is uncertain. Using the 2-[18F]fluoro-2-deoxy-D-glucose and PET method, we determined the local cerebral metabolic rate of glucose utilization in seven patients with palatal myoclonus (following stroke or infection, or idiopathic), one patient with oculopalatal myoclonus (following a stroke affecting the brainstem), and nine normal subjects. The metabolism of glucose in the medulla of the patients with palatal myoclonus was significantly greater than that of the normal subjects. This may well have been due to increased metabolism of the inferior olivary nuclei. Glucose metabolism in the medulla of the patient with oculopalatal myoclonus was normal. These findings suggest that the inferior olivary nuclei, or a region of the brainstem encompassing the inferior olivary nuclei, are hypermetabolic in palatal myoclonus and may be the generators of the involuntary movements in palatal myoclonus.

Visually Induced Eye Movements in Wallenberg's Syndrome

Eighteen patients with Wallenberg's syndrome were investigated concerning visually induced eye movements. All results were analysed quantitatively using a computer. In 16 out of 18 patients, OKN slow-phase velocities were impaired, in the remaining 2 patients they were normal. Patients who showed impaired OKN were classified into two groups according to directional asymmetry of OKN impairment. In 7 out of the 16 patients, slow-phases toward the lesion side were predominantly impaired in contrast to the slow-phases toward the intact side (group A). In the remaining 9 patients, slow-phases toward the intact side were predominantly impaired (group B). The smooth pursuit showed the same asymmetry as the OKN slow-phase, except, in 4 patients who showed normal smooth pursuit. All patients showed reduced visual suppression of caloric nystagmus during the slow-phase of nystagmus toward the lesion side, except 3 patients who showed normal visual suppression in both directions. CT scan failed to detect either the brainstem or the cerebellar lesions in any cases, but MRI performed on the most recent cases demonstrated the infarctions clearly. These findings suggest that infarctions are localized in the medulla in the patients of group A, but extend to the cerebellum as well as to the medulla in patients of group B.