Papers by William Pendlebury
J Neuropathol Exp Neurol, 1989
Acta Neurol Scand, 2009
We report three patients who exhibited an unusual clinical course of chronic inflammatory demyeli... more We report three patients who exhibited an unusual clinical course of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in which mononeuropathic limb weakness developed 2, 11 and 23 years, respectively, before the development of generalized polyradiculoneuropathy. The eventual diagnosis remained uncertain until other causes of neuropathy were excluded, and the clinical disorder progressed to involve the other limbs. Focal or regional variants of CIDP suggest that the pathologic, and perhaps the immunologic, abnormalities can be localized and selective for prolonged periods of time. Although this clinical variant seems to account for a small number of CIDP cases, its recognition may aid in making an early diagnosis.
International Psychogeriatrics Ipa, Dec 1, 2000
The purpose of this study was to evaluate the utility (i.e., positive and negative predictive val... more The purpose of this study was to evaluate the utility (i.e., positive and negative predictive value) of the 7 Minute Screen in identifying patients with probable Alzheimer's disease (AD) in a primary care practice. A second objective was to estimate the number of undiagnosed AD patients in a typical primary care practice. One hundred thirty-seven successive admissions (96%) of patients over the age of 60 to a primary care practice over a 53-day period who completed informed consent documents were administered the 7 Minute Screen. All patients who screened positive (n = 13) and a random sample of those who screened negative (n = 26) returned for full diagnostic evaluation. Positive predictive value (PPV) and negative predictive value (NPV) of the 7 Minute Screen were determined using the criterion standard of clinical diagnosis established by examination, history, and laboratory studies. Test-retest reliability and time for administration were also determined. Of the 137 patients evaluated, 13 screened positive and 124 screened negative. Eleven of the 13 patients who screened positive were willing to return to the primary care practice for follow-up evaluation. A random sample of 26 patients who screened negative all agreed to return for follow-up evaluation. Of the 11 patients who screened positive and who returned for evaluation, 10 were subsequently diagnosed with probable AD. The remaining patient was diagnosed with mixed dementia. The caregivers of the two patients who refused to return were contacted and both indicated that the patients were having significant cognitive problems as verified by an activities of daily living scale. Of the 26 patients who screened negative, 25 were judged to be cognitively normal and the 26th was judged to have mild cognitive impairment. In successive admissions of patients over the age of 60 in a primary care practice, the 7 Minute Screen showed a PPV of 91% and an NPV of 96% in identifying patients who were subsequently identified with AD or other dementing disorder. These data suggest that this may be a useful instrument in identifying patients who should undergo diagnostic evaluation for AD and other dementing disorders. Additionally, extrapolation from the data in this practice suggests that there may be between 75 and 100 AD patients in the typical primary care practice, many of whom may not be diagnosed.
Synapse, Sep 1, 2003
Synaptological characteristics of synapses between axonal boutons of the trigeminal mesencephalic... more Synaptological characteristics of synapses between axonal boutons of the trigeminal mesencephalic nucleus (Vme) neurons and the hypoglossal nucleus (XII) motoneurons (MNs) were studied using biotinylated dextran amine (BDA) anterograde labeling combined with horseradish peroxidase (HRP) retrograde transport in the rat. BDA was initially iontophoresed into Vme unilaterally and 7 days later HRP was injected into the anterior two-thirds of the ipsilateral tongue. After histochemical reactions, BDA anterogradely labeled boutons were seen to appose closely to somata and dendrites of HRP retrogradely labeled MNs in XII by light microscopy. A total of 212 BDA-labeled Vme boutons were examined ultrastructurally, which had an average diameter of 1.3 +/- 0.4 microm and contain small clear spherical vesicles. Eighty-eight percent of Vme boutons (187/212) synapsed on dendrites of HRP-labeled XII MNs. Twenty-five Vme boutons (25/212, 12%) made synapses with somata of HRP-labeled XII MNs. Thirty-five percent (74/212) of BDA-labeled Vme boutons were also contacted by unlabeled P-type terminals. Presynaptic P-type terminals contained spherical (47%, 35/74), pleomorphic (43%, 32/74), and flattened (10%, 7/74) synaptic vesicles. Thus, P-type terminals (as a presynaptic element), BDA-labeled Vme boutons, and XII MNs constitute axoaxodendritic and axoaxosomatic synaptic triads. There are four types of synaptic microcircuits in XII neuropil: synaptic convergence, synaptic divergence, presynaptic inhibition synaptic circuits, and feedforward regulation circuits. This detailed ultrastructure examination of the synaptic organization between Vme neurons and XII MNs provides insights into the synaptic mechanisms of the trigeminal proprioceptive afferents involved in the jaw-tongue reflex and coordination during oral motor behaviors.
Case Reports in Neurological Medicine, 2015
We describe a case with a false-negative PCR-based analysis for JC virus in cerebrospinal fluid (... more We describe a case with a false-negative PCR-based analysis for JC virus in cerebrospinal fluid (CSF) in a patient with clinical and radiological findings suggestive of progressive multifocal leukoencephalopathy (PML) who was on chronic immunosuppressive therapy for rheumatoid arthritis. Our patient developed rapidly progressive global decline with clinical and radiographic findings suggestive of PML, but JC virus PCR in CSF was negative. The patient passed away 3 months from the onset of her neurological symptoms. Autopsy confirmed the diagnosis of PML with presence of JC-polyoma virus by immunohistochemical staining. This case highlights the potential of false-negative JC virus PCR in CSF when radiographic and clinical features are suggestive of "possible PML. " We review the plausible causes of potential false-negative CSF results and suggest that when the clinical presentation is suspicious for PML repeat CSF analysis utilizing ultrasensitive PCR assay and subsequent brain biopsy should be considered if CSF remains negative. Additionally, appropriate exclusion of other neurologic conditions is essential.
Synapse, 2003
Synaptological characteristics of synapses between axonal boutons of the trigeminal mesencephalic... more Synaptological characteristics of synapses between axonal boutons of the trigeminal mesencephalic nucleus (Vme) neurons and the hypoglossal nucleus (XII) motoneurons (MNs) were studied using biotinylated dextran amine (BDA) anterograde labeling combined with horseradish peroxidase (HRP) retrograde transport in the rat. BDA was initially iontophoresed into Vme unilaterally and 7 days later HRP was injected into the anterior two-thirds of the ipsilateral tongue. After histochemical reactions, BDA anterogradely labeled boutons were seen to appose closely to somata and dendrites of HRP retrogradely labeled MNs in XII by light microscopy. A total of 212 BDA-labeled Vme boutons were examined ultrastructurally, which had an average diameter of 1.3 +/- 0.4 microm and contain small clear spherical vesicles. Eighty-eight percent of Vme boutons (187/212) synapsed on dendrites of HRP-labeled XII MNs. Twenty-five Vme boutons (25/212, 12%) made synapses with somata of HRP-labeled XII MNs. Thirty-five percent (74/212) of BDA-labeled Vme boutons were also contacted by unlabeled P-type terminals. Presynaptic P-type terminals contained spherical (47%, 35/74), pleomorphic (43%, 32/74), and flattened (10%, 7/74) synaptic vesicles. Thus, P-type terminals (as a presynaptic element), BDA-labeled Vme boutons, and XII MNs constitute axoaxodendritic and axoaxosomatic synaptic triads. There are four types of synaptic microcircuits in XII neuropil: synaptic convergence, synaptic divergence, presynaptic inhibition synaptic circuits, and feedforward regulation circuits. This detailed ultrastructure examination of the synaptic organization between Vme neurons and XII MNs provides insights into the synaptic mechanisms of the trigeminal proprioceptive afferents involved in the jaw-tongue reflex and coordination during oral motor behaviors.
Psychology and Aging, 1995
Previous studies demonstrated that patients with Alzheimer's disease (AD) do not acquire ... more Previous studies demonstrated that patients with Alzheimer's disease (AD) do not acquire the classically conditioned eyeblink response. These studies, however, were only tested over a single conditioning session and, hence, raise the question of whether AD patients are capable of acquiring the response if sufficient training is given. This question may be of some importance whether AD patients can ultimately acquire the response has implications for the underlying neurobiological deficit in disrupted conditioning in AD. This study tested AD patients and age-matched controls over 4 days. As in previous studies, AD patients performed significantly worse than controls on Day 1, but by Day 4, they were not significantly different from controls. Subsequent testing indicated that these effects were not due to nonassociative variables such as changes in sensitivity to stimuli or disruption of the motor response. Also, it was reported that neither AD patients nor controls showed any evidence of acquisition in an explicitly unpaired paradigm, suggesting that neither pseudoconditioning nor sensitization is contributory. Data are discussed in terms of the possible role of the hippocampus in mediating conditioning deficits in AD patients.
Neuroscience, 1989
Aluminum-induced neurofibrillary degeneration in rabbits is known to affect particular population... more Aluminum-induced neurofibrillary degeneration in rabbits is known to affect particular populations of neurons. The neurotransmitter alterations which accompany aluminum neurofibrillary degeneration were examined in order to assess how closely they mimic those of Alzheimer's disease. There was a significant reduction in choline acetyltransferase activity in entorhinal cortex and hippocampus as well as significant reductions in cortical concentrations of serotonin and norepinephrine in the aluminum-treated rabbits. Significant reductions in glutamate, aspartate and taurine were found in frontoparietal and posterior parietal cortex. Concentrations of GABA were unchanged in cerebral cortex. Both substance P and cholecystokinin immunoreactivity were significantly reduced in entorhinal cortex but there were no significant changes in somatostatin, neuropeptide Y and vasoactive intestinal polypeptide. The five neuropeptides were unaffected in striatum, thalamus, cerebellum and brainstem. Neurochemical changes were found in the regions with the most neurofibrillary degeneration while regions with little or no neurofibrillary degeneration were unaffected. The reductions in choline acetyltransferase activity, serotinin and noradrenaline suggest that some neuronal populations preferentially affected in Alzheimer's disease are also affected by aluminum-induced neurofibrillary degeneration; however, the cortical somatostatin deficit which is a feature of Alzheimer's disease is not replicated in the aluminum model.
Neuroscience, 1989
Neurofibrillary tangles in Alzheimer's disease show a predilection for cortical pyramidal and sub... more Neurofibrillary tangles in Alzheimer's disease show a predilection for cortical pyramidal and subcortical projection neurons.
Neurology, 2003
The authors describe a patient with an isolated, gadolinium-enhancing, biopsy-proven focus of tum... more The authors describe a patient with an isolated, gadolinium-enhancing, biopsy-proven focus of tumefactive demyelination. There was marked clinical improvement with plasma exchange after failure of high-dose i.v. corticosteroids. The post-treatment clinical course correlated with decreasing enhancement and lesion size on MRI. This patient's rapid clinical and MRI response suggests that plasma exchange may be beneficial in this disorder, and could perhaps serve as a diagnostic tool to avoid the need for brain biopsy.
Neurobiology of Aging, 1990
Rabbits were classically conditioned to emit an eyeblink conditioned response (CR) to electrical ... more Rabbits were classically conditioned to emit an eyeblink conditioned response (CR) to electrical stimulation (ESB) of the medial geniculate nucleus (MGN) paired with a corneal air puff until they attained a criterion of two consecutive days of greater than 90% CRs. They then received intraventricular injections of 1% AlCl3, HCL, or normal saline. Ten days postinjection, each animal underwent a retention test consisting of 50 ESB alone presentations. Whereas all saline and HCL animals gave at least 90% CRs during retention, no aluminum rabbit emitted more than 30% CRs. Considered with the results of previous work, these data suggest that aluminum-induced neurofibrillary degeneration disrupts retention of the CR by affecting central associative processes.
Neurobiology of Aging, 1991
One of the primary features of Alzheimer's disease (AD) is a disorder of memory. Although... more One of the primary features of Alzheimer's disease (AD) is a disorder of memory. Although considerable effort has been devoted to characterizing this memory disorder, simple forms of memory such as classical (Pavlovian) conditioning have not been studied. The prevailing view has been that these simple forms of memory are not affected in AD. These forms of memory, however, may be of particular interest because they are beginning to be well understood at the neurobiological level. Because of this, when memory disorders are detected, it may be possible to specify their neurobiological substrate. We now report that classical conditioning of the eyeblink response is disrupted in AD patients compared to age-matched controls. This deficit in conditioning is not due to nonassociative factors such as changes in sensitivity to stimuli or disruption of the motor response. The results are considered in terms of using simple forms of memory to help generate hypotheses regarding the neurobiology of age-related memory disorders.
Muscle & Nerve, 1991
A patient with inclusion body myositis (IBM) is presented. Unusual aspects of this case include a... more A patient with inclusion body myositis (IBM) is presented. Unusual aspects of this case include a myopathy of 36 years duration, severe dysphagia due to cricopharyngeus muscle dysfunction, improvement with cricopharyngeus myotomy, and a diagnostic cricopharyngeus muscle biopsy.
Laboratory Investigation, 2008
Proteinaceous deposits are occasionally encountered in surgically obtained biopsies of the nervou... more Proteinaceous deposits are occasionally encountered in surgically obtained biopsies of the nervous system. Some of these are amyloidomas, although the precise nature of other cases remains uncertain. We studied 13 cases of proteinaceous aggregates in clinical specimens of the nervous system. Proteins contained within laser microdissected areas of interest were identified from tryptic peptide sequences by liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). Immunohistochemical studies for immunoglobulin heavy and light chains and amyloidogenic proteins were performed in all cases. Histologically, the cases were classified into three groups: 'proteinaceous deposit not otherwise specified' (PDNOS) (n ¼ 6), amyloidoma (n ¼ 5), or 'intracellular crystals' (n ¼ 2). LC-MS/MS demonstrated the presence of l, but not k, light chain as well as serum amyloid P in all amyloidomas. l-Light-chain immunostaining was noted in amyloid (n ¼ 5), although demonstrable monotypic lymphoplasmacytic cells were seen in only one case. Conversely, in PDNOS k, but not l, was evident in five cases, both light chains being present in a single case. In three cases of PDNOS, a low-grade B-cell lymphoma consistent with marginal zone lymphoma was present in the brain specimen (n ¼ 2) or spleen (n ¼ 1). Lastly, in the 'intracellular crystals' group, the crystals were present within CD68 þ macrophages in one case wherein k-light chain was found by LC-MS/MS only; the pathology was consistent with crystalstoring histiocytosis. In the second case, the crystals contained immunoglobulin G within CD138 þ plasma cells. Our results show that proteinaceous deposits in the nervous system contain immunoglobulin components and LC-MS/MS accurately identifies the content of these deposits in clinical biopsy specimens. LC-MS/MS represents a novel application for characterization of these deposits and is of diagnostic utility in addition to standard immunohistochemical analyses.
Journal of the Neurological Sciences, 1987
Giant axonal neuropathy (GAN) is a rare autosomal recessive childhood disorder characterized by a... more Giant axonal neuropathy (GAN) is a rare autosomal recessive childhood disorder characterized by a peripheral neuropathy and features of central nervous system involvement. Typically seen are distal axonal swellings filled with 8-10 nm in diameter neurofilaments in central and peripheral axons, and intermediate filament collections in several other cell types. Many neurotoxins produce a morphologically similar neuropathy in humans and experimental animals. Defective nerve fiber energy metabolism has been postulated as a cause in these toxic neuropathies. It is possible that GAN represents an inborn error of metabolism of enzyme-linked sulfhydryl containing proteins, resulting in impaired production of energy necessary for the normal organization of intermediate filaments.
Journal of Neurosurgery, 2002
Journal of Neurosurgery, 1991
Journal of Neuropathology and Experimental Neurology, 1984
Journal of Neuropathology and Experimental Neurology, 1995
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Papers by William Pendlebury