Neurogenic Deficits Research Articles

Regional Comparison of the Neurogenic Effects of CNTF-Derived Peptides and Cerebrolysin in AβPP Transgenic Mice

Adult neurogenesis, the production of new neurons in certain brain regions, is known to decrease with age and the loss of neurogenic potential has been implicated in Alzheimer's disease (AD), a leading cause of dementia in the elderly. Cerebrolysin (CBL) has been shown to increase neurogenesis in models of stroke and AD. CBL is composed of small peptides with activity similar to neurotrophic factors including ciliary neurotrophic factor (CNTF), which may mediate its neurogenic effects. This study compares the effects of CBL and two peptides with corresponding to an active region of CNTF (Peptide 6 and 6A) across neurogenic brain regions in amyloid-β protein precursor (AβPP) transgenic (tg) mice. Both CBL and Peptides 6 and 6A were able to increase the numbers of neuroblasts (DCX+ cells) and BrdU+ cells in a regionally specific manner across the subventricular zone, olfactory bulb, and hippocampus. The increased generation of new cells and cell survival in animals treated with Peptides 6 and 6A was accompanied by an increase in PCNA+ cells. In contrast, AβPP tg mice treated with CBL displayed reduced levels of TUNEL staining, while levels of PCNA were unaltered. Collectively these results demonstrate that while CBL and Peptides 6 and 6A all potentiate neurogenesis in the AβPP tg mice, their relative modes of action may differ with CBL associated with reduced apoptosis and Peptides 6 and 6A working by augmenting cell proliferation. These results are consistent with a potential therapeutic relevance for Peptides 6 and 6A in AD and other disorders characterized by neurogenic deficits.

Rapid Ischemic Preconditioning with a Short Reperfusion Time Prevents Delayed Paraplegia in a Rabbit Model

Surgery for thoracic and thoracoabdominal aortic aneurysms can be complicated by a significant incidence of neurogenic deficits due to spinal cord ischemia. In this study, we investigated whether ischemic preconditioning (IPC) improves neurologic outcome in a rabbit model. Forty rabbits underwent infrarenal aortic occlusion. The IPC group (n = 20) had 10 minutes of aortic occlusion to induce spinal cord ischemia, 40 minutes of reperfusion, and 30 minutes of ischemia, whereas the control group (n = 20) had only 30 minutes of ischemia. Tarlov scoring (0, paraplegia; 4, normal) was used to evaluate neurologic functions 7 days later, and spinal cord segments (L4-L6) were stained with hematoxylin and eosin for histologic evaluation. Complete paraplegia (grade 0) occurred in 15 (75%) of the 20 control animals, whereas in the IPC group, 13 (65%) of 20 animals were completely normal (grade 4) (P < .05). IPC is beneficial for protecting against neurologic damage after transient aortic occlusion in a rabbit model; however, the protective mechanisms are not clear.

Allopregnanolone restores hippocampal-dependent learning and memory and neural progenitor survival in aging 3xTgAD and nonTg mice

We previously demonstrated that allopregnanolone (APα) increased proliferation of neural progenitor cells and reversed neurogenic and cognitive deficits prior to Alzheimer's disease (AD) pathology (Wang, J.M., Johnston, P.B., Ball, B.G., Brinton, R.D., 2005. The neurosteroid allopregnanolone promotes proliferation of rodent and human neural progenitor cells and regulates cell-cycle gene and protein expression. J. Neurosci. 25, 4706–4718; Wang, J.M., Singh, C., Liu, L., Irwin, R.W., Chen, S., Chung, E.J., Thompson, R.F., Brinton, R.D., 2010. Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer's disease. Proc. Natl. Acad. Sci. U. S. A. 107, 6498–6503). Herein, we determined efficacy of APα to restore neural progenitor cell survival and associative learning and memory subsequent to AD pathology in male 3xTgAD mice and their nontransgenic (nonTg) counterparts. APα significantly increased survival of bromodeoxyuridine positive (BrdU+) cells and hippocampal-dependent associative learning and memory in 3xTgAD mice in the presence of intraneuronal amyloid beta (Aβ) whereas APα was ineffective subsequent to development of extraneuronal Aβ plaques. Restoration of hippocampal-dependent associative learning was maximal by the first day and sustained throughout behavioral training. Learning and memory function in APα-treated 3xTgAD mice was 100% greater than vehicle-treated and comparable to maximal normal nonTg performance. In aged 15-month-old nonTg mice, APα significantly increased survival of bromodeoxyuridine-positive cells and hippocampal-dependent associative learning and memory. Results provide preclinical evidence that APα promoted survival of newly generated cells and restored cognitive performance in the preplaque phase of AD pathology and in late-stage normal aging.

Unusual clinical presentation and neuropathology in two subjects with fused-in sarcoma (FUS) positive inclusions

We report two unusual autopsy cases with frontotemporal lobar degeneration (FTLD) that were hyperphosphorylated-tau- and TAR DNA binding protein 43 (TDP-43)- negative. The behavioral symptoms in both cases were compatible with frontotemporal dementia, but they exhibited more prominent speech and language related symptoms than previously reported. Moreover, they displayed a short duration of the disease; the male case had a disease onset age of 45 years, and duration of 5 years, and the female case suffered even shorter disease duration and a later onset of the symptoms, at the age of 67 years. Moreover, the motor functions had deteriorated in different ways in these cases. The male patient showed progressive motor symptoms, weakness of extremities and bulbar muscles suggesting motor neuron disease with a muscle biopsy supporting neurogenic deficits, whereas the female patient exhibited dyskinesias and tremor with progressive swallowing disorders. The father of the male case displayed dementia of similar type at the age of 68 years. In both cases, neuropathological examination showed fused-in sarcoma (FUS)-positive pathology. The male patient had intensely FUS-positive cytoplasmic and intranuclear inclusions that resembled the characteristics previously reported in FTLD FUS, whereas the female patient did not exhibit any cytoplasmic inclusions but had roundish, dense FUS-positive intranuclear inclusions. She also displayed a plethora of other pathologies including α-synuclein, hyperphosphorylated-tau, β-amyloid aggregation and some neuronal polyglutamine aggregation (1C2) but no well-demarcated inclusions were observed. We conclude that clinical phenotypes of FUS pathologies also include elderly patients and are more variable with motor and speech disorders than previously reported.

Reduction in hippocampal neurogenesis after social defeat is long-lasting and responsive to late antidepressant treatment

Major depressive disorder is a chronic disabling disease, often triggered and exacerbated by stressors of a social nature. Hippocampal volume reductions have been reported in depressed patients. In support of the neurogenesis theory of depression, in several stress-based animal models of depression, adult hippocampal neurogenesis was reduced and subsequently rescued by parallel antidepressant treatment. Here, we investigated whether repeated social defeat and subsequent individual housing for 3 months induces long-lasting changes in adult hippocampal neurogenesis in rats, and whether these can be normalized by late antidepressant treatment, as would match human depression. Neurogenesis was analysed by stereological quantification of the number of immature doublecortin (DCX)-immunopositive cells, in particular young (class I) and more mature (class II) DCX(+) cells, to distinguish differential effects of stress or drug treatment on these subpopulations. Using this social defeat paradigm, the total DCX(+) cell number was significantly reduced. This was most profound for older (class II) DCX(+) cells with long apical dendrites, whereas younger, class I cells remained unaffected. Treatment with the broad-acting tricyclic antidepressant imipramine, only during the last 3 weeks of the 3-month period after social defeat, completely restored the reduction in neurogenesis by increasing both class I and II DCX(+) cell populations. We conclude that despite the lack of elevated corticosterone plasma levels, neurogenesis is affected in a lasting manner by a decline in a distinct neuronal population of more mature newborn cells. Thus, the neurogenic deficit induced by this social defeat paradigm is long-lasting, but can still be normalized by late imipramine treatment.

Moderate fetal alcohol exposure impairs neurogenic capacity of murine neural stem cells isolated from the adult subventricular zone

Gestational alcohol exposure leads to a spectrum of neurological symptoms which range from severe mental retardation caused by high dose exposure, to subtle cognitive and neuropsychiatric symptoms caused by low-to-moderate doses. We and other investigators have demonstrated that exposure to moderate levels of alcohol throughout gestation leads to impaired neurogenesis in the adult hippocampus, although the mechanisms by which this occurs are not known. To begin to distinguish cell-intrinsic from microenvironmental contributions to impaired adult neurogenesis, we isolated neural stem progenitor cells (NSPCs) from the adult SVZ of mice exposed to moderate levels of alcohol throughout gestation. We found that NSPCs isolated from fetal alcohol exposed (FAE) mice displayed reduced neurosphere formation in culture, as assessed by a serial passage neurosphere assay, and reduced neuronal differentiation upon growth factor withdrawal. These studies suggest that gestational alcohol exposure leads to long-lasting NSPC-intrinsic dysregulation, which may underlie in vivo neurogenic deficits.

Increased BMP6 Levels in the Brains of Alzheimer's Disease Patients and APP Transgenic Mice Are Accompanied by Impaired Neurogenesis

During aging and in the progression of Alzheimer's disease (AD), synaptic plasticity and neuronal integrity are disturbed. In addition to the alterations in plasticity in mature neurons, the neurodegenerative process in AD has been shown to be accompanied by alterations in neurogenesis. Members of the bone morphogenetic protein (BMP) family of growth factors have been implicated as important regulators of neurogenesis and neuronal cell fate determination during development; however, their role in adult neurogenesis and in AD is less clear. We show here by qRT-PCR analysis that BMP6 mRNA levels were significantly increased in the hippocampus of human patients with AD and in APP transgenic mice compared to controls. Immunoblot and immunohistochemical analyses confirmed that BMP6 protein levels were increased in human AD brains and APP transgenic mouse brains compared to controls and accumulated around hippocampal plaques. The increased levels of BMP6 were accompanied by defects in hippocampal neurogenesis in AD patients and APP transgenic mice. In support of a role for BMP6 in defective neurogenesis in AD, we show in an in vitro model of adult neurogenesis that treatment with amyloid-β(1-42) protein (Aβ) resulted in increased expression of BMP6, and that exposure to recombinant BMP6 resulted in reduced proliferation with no toxic effects. Together, these results suggest that Aβ-associated increases in BMP6 expression in AD may have deleterious effects on neurogenesis in the hippocampus, and therapeutic approaches could focus on normalization of BMP6 levels to protect against AD-related neurogenic deficits.

Correction for Wang et al., Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer's disease

Correction for Wang et al., Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer's disease

Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer's disease

Our previous analyses showed that allopregnanolone (APalpha) significantly increased proliferation of rodent and human neural progenitor cells in vitro. In this study, we investigated the efficacy of APalpha to promote neurogenesis in the hippocampal subgranular zone (SGZ), to reverse learning and memory deficits in 3-month-old male triple transgenic mouse model of Alzheimer's (3xTgAD) and the correlation between APalpha-induced neural progenitor cell survival and memory function in 3xTgAD mice. Neural progenitor cell proliferation was determined by unbiased stereological analysis of BrdU incorporation and survival determined by FACS for BrdU+ cells. Learning and memory function was assessed using the hippocampal-dependent trace eye-blink conditioning paradigm. At 3 months, basal level of BrdU+ cells in the SGZ of 3xTgAD mice was significantly lower relative to non-Tg mice, despite the lack of evident AD pathology. APalpha significantly increased, in a dose-dependent manner, BrdU+ cells in SGZ in 3xTgAD mice and restored SGZ proliferation to normal magnitude. As with the deficit in proliferation, 3xTgAD mice exhibited deficits in learning and memory. APalpha reversed the cognitive deficits to restore learning and memory performance to the level of normal non-Tg mice. In 3xTgAD mice, APalpha-induced survival of neural progenitors was significantly correlated with APalpha-induced memory performance. These findings suggest that early neurogenic deficits, which were evident before immunodetectable Abeta, may contribute to the cognitive phenotype of AD, and that APalpha could serve as a regenerative therapeutic to prevent or delay neurogenic and cognitive deficits associated with mild cognitive impairment and Alzheimer's disease.

Metformin therapy to reduce weight gain and visceral adiposity in children and adolescents with neurogenic or myogenic motor deficit

The aim of this randomized, placebo-controlled study was to explore the effect of metformin in children with a neurogenic or myogenic motor deficit, who are therefore prone to develop overweight, adiposity, and insulin resistance. Study participants (n = 42) had a mean age of 15.5 yr, a short stature (height -2.4 SD), a relatively high BMI (+1.7 SD), and a high body fat fraction (41.9% or +2.8 SD). Abdominal CT confirmed the high fat mass and disclosed a high fraction of visceral fat. As expected, insulin resistance was increased. As compared to placebo, metformin intake for 6 months exerted an insulin sensitizing effect and lowered weight (mean difference of 2 kg within 6 months, p = 0.007) and BMI (p = 0.016). Weight loss appeared to be primarily due to loss of visceral fat ( approximately 20% vs. placebo; p < 0.0001). Results were similar across diagnostic subgroups. In conclusion, metformin treatment for 6 months was associated with a rise in insulin sensitivity and with a reduction of visceral adiposity in children and adolescents with a primary muscle disorder or with a neural tube defect. These findings suggest that insulin resistance underpins, at least partly, the overweight and visceral adiposity of these patients, who are not necessarily obese.

Epigenetic Regulation of the Stem Cell Mitogen Fgf-2 by Mbd1 in Adult Neural Stem/Progenitor Cells

Whether and how mechanisms intrinsic to stem cells modulate their proliferation and differentiation are two central questions in stem cell biology. Although exogenous basic fibroblast growth factor 2 (FGF-2/Fgf-2) is commonly used to expand adult neural stem/progenitor cells (NSPCs) in vitro, we do not yet understand the functional significance or the molecular regulation of Fgf-2 expressed endogenously by adult NSPCs. We previously demonstrated that methylated CpG binding protein 1 (MBD1/Mbd1) is a transcriptional repressor of Fgf-2 and is enriched in adult brains. Mbd1 deficiency in mice selectively affected adult neurogenesis and the differentiation of NSPCs. Here we show that an Mbd1 and DNA methylation-mediated epigenetic mechanism regulated the expression of stem cell mitogen Fgf-2 in adult NSPCs. Mbd1 bound to the Fgf-2 promoter and regulates its expression in adult NSPCs. In the absence of functional Mbd1, the Fgf-2 promoter was hypomethylated, and treatment with a DNA methylation inhibitor resulted in increased Fgf-2 expression in adult NSPCs. We further demonstrated that both acute knockdown of Mbd1 or overexpression of Fgf-2 in adult NSPCs inhibited their neuronal differentiation, which could be responsible for the neurogenic deficits observed in Mbd1-deficient mice. These data indicate that intrinsic epigenetic mechanisms play critical roles in the regulation of adult NSPC functions.

P-076: Estrogen receptor-selective ligands regulate ApoE expression and neurogenesis in 3xTgAD mouse hippocampus

The single amino acid substitutions of apolipoprotein E (ApoE) drive late-onset Alzheimer's disease (AD) in opposite directions. ApoE2 and ApoE3 are protectors from AD progression, but ApoE4 is a major risk factor for AD progression. Population-based investigations indicated that the ApoE4 allele is a major risk factor for ∼50% of AD cases in the United States. Recent data indicated that ectopic expression of ApoE4 increased Amyloid β (Aβ) deposition and burden, while expression of ApoE2/3 markedly reduced the AD pathology progression in DPAPP mouse hippocampus by intracerebral administration of lentiviral vectors expressing the three common human ApoE isoforms. The above data strongly support the idea that regulation of the levels of ApoE in human subjects is a powerful AD-prevention stratagem. We recently demonstrated that ApoE expression could be differentially regulated by estrogen receptor selective ligands in rat hippocampal neurons in vitro and in vivo. This study investigated the impact of ER-selective ligands on ApoE expression and neurogenesis in 3xTgAD mouse SGZ. Methods: ApoE expression, neurogenesis and AD progression in LaFerla 3xTgAD and non-Tg mouse were measured by Western blot, IHC and unbiased stereology. 1) ER-selective ligands differentially regulated ApoE expression in mouse and rat hippocampus; 2) 17β-estradiol reduced Aβ burden in 3xTgAD mouse hippocampus; 3) 17β-estradiol and propyl pyrazole triol (PPT, an ERα-selective ligand which increases ApoE expression) reversed the neurogenic deficits, while diarylpropionitrile (DPN, an ERβ ligand which reduces ApoE expression) had no effect on neurogenesis in the SGZ of 3xTgAD mouse. This study suggests, when ERα- and ERβ-selective ligands are applied to ApoE2/3 and ApoE4 allelic carriers, respectively, that the ERα-specific ligand will reduce AD pathology and enhance neurogenesis in ApoE3/AD carriers, while the ERβ-specific ligand will reduce AD pathology and increase neurogenesis in ApoE4/AD carriers.

Structural basis of neurogenic bladder dysfunction. I. Methods of prospective ultrastructural study and overview of the findings.

We standardize procedures for ultrastructural study of detrusor smooth muscle and intrinsic nerves in neurogenic bladder dysfunction in the human, and present an overview of the findings. The study included 18 female and 33 male patients 7 to 96 years old. They had neurogenic bladder dysfunction with hyperreflexia for less than 1 to 43 years, resulting from upper motoneuron lesions (spinal cord injury 25, brain disorder 17) or combined upper and lower motoneuron deficit (meningomyelocele 9). Endoscopic or open bladder biopsies were processed for ultrastructural study of detrusor smooth muscle and intrinsic neural elements. Qualitative morphologic criteria of muscle cell arrangement, degeneration and cell-cell contacts, as well as those of degeneration and regeneration of intrinsic neural elements are defined. Five biopsies from the brain disorder group had insufficient smooth muscle and were excluded from study. The remaining 46 biopsies were evaluated by electron microscopy, and all displayed the complete dysjunction pattern of detrusor overactivity. Most displayed degeneration and regeneration of intrinsic axons but disproportionately limited muscle cell degeneration, irrespective of detrusor contractility. The brain disorder group biopsies displayed many more ultrastructurally normal axons than the meningomyelocele and spinal cord injury group biopsies (median 33% versus 8% or less). Upper motoneuron neurogenic bladder dysfunction in humans is associated with intrinsic neuromuscular defects in the detrusor. Ultrastructural features of these defects suggest morphologic markers that not only may distinguish neuropathic from nonneuropathic bladder dysfunction, but also may point to the anatomical level of the neurogenic deficit.

Structural Basis of Neurogenic Bladder Dysfunction. I. Methods of Prospective Ultrastructural Study and Overview of the Findings

We standardize procedures for ultrastructural study of detrusor smooth muscle and intrinsic nerves in neurogenic bladder dysfunction in the human, and present an overview of the findings.The study included 18 female and 33 male patients 7 to 96 years old. They had neurogenic bladder dysfunction with hyperreflexia for less than 1 to 43 years, resulting from upper motoneuron lesions (spinal cord injury 25, brain disorder 17) or combined upper and lower motoneuron deficit (meningomyelocele 9). Endoscopic or open bladder biopsies were processed for ultrastructural study of detrusor smooth muscle and intrinsic neural elements. Qualitative morphologic criteria of muscle cell arrangement, degeneration and cell-cell contacts, as well as those of degeneration and regeneration of intrinsic neural elements are defined.Five biopsies from the brain disorder group had insufficient smooth muscle and were excluded from study. The remaining 46 biopsies were evaluated by electron microscopy, and all displayed the complete dysjunction pattern of detrusor overactivity. Most displayed degeneration and regeneration of intrinsic axons but disproportionately limited muscle cell degeneration, irrespective of detrusor contractility. The brain disorder group biopsies displayed many more ultrastructurally normal axons than the meningomyelocele and spinal cord injury group biopsies (median 33% versus 8% or less).Upper motoneuron neurogenic bladder dysfunction in humans is associated with intrinsic neuromuscular defects in the detrusor. Ultrastructural features of these defects suggest morphologic markers that not only may distinguish neuropathic from nonneuropathic bladder dysfunction, but also may point to the anatomical level of the neurogenic deficit.

Micturition and the Sacral Reflex Arc: Lessons from Electrophysiological Techniques

Electrophysiological techniques applied either for diagnostic or therapeutic reasons have contributed to elucidation of the neurocontrol of micturition. But the ability of electrophysiological diagnostic tests to reveal neurogenic involvement in patients suffering from lower urinary tract dysfunction is limited, and has been overestimated. Furthermore, the correlation between a proven neurogenic deficit and the consecutive dysfunction is complex. The electrophysiological tests, however, may also be applied for testing the central nervous system integrative function, such as in testing reflex thresholds, excitability levels of motor nuclei, etc. The use of electrical stimulation for therapeutic purposes has instigated much physiological research. Insights related to micturition neurocontrol, as for instance that afferent inputs from lumbosacral and vesical sensory fibres modulate the micturition threshold, are being therapeutically exploited. It is expected that further use of electrophysiological techniques, being complementary to functional neuroimaging, will clarify particularly the temporal aspects of neurocontrol mechanisms involved in micturition.

Functional neck dissection: cure and functional results.

In this study, the cure and functional results of 133 functional neck dissections performed between 1992-1997 in Erciyes University Medical Faculty were evaluated. The overall recurrence rate was three per cent. This rate was 1.4 per cent for elective functional neck dissections and five per cent for curative functional neck dissections. Electromyographic studies showed that there was severe neurogenic deficit in the trapezius muscle of seven patients (12.5 per cent), and in the sternocleidomastoid muscle of 12 patients (21.4 per cent) among 56 randomly selected patients. In all cases, the flow rate and diameter of the internal jugular vein was found to be normal by Doppler ultrasonography. The results of this study showed that functional neck dissection is a reliable technique for obtaining a high cure rate and functional results.

Prevention of spinal cord ischemia by selective intercostal arterial infusion of prostaglandin E1

Purpose: A new protective method against the spinal cord ischemia that occurs during aortic clamping was investigated in dogs. Oxygenated blood containing prostaglandin E 1 (PGE 1) was administered at the clamped aortic segment, and the effect was evaluated by measurement of the sensory evoked spinal potential (SESP). Methods: In 30 dogs, a thoracotomy was made with dissection of the thoracic aorta. After intravenous heparin (100 units/kg) was administered, the proximal and distal descending thoracic aortas were cross-clamped for 60 minutes. Group A (n = 10) received oxygenated blood at the rate of 1.0 ml/kg/min. Groups B (n = 10) and C (n = 10) received oxygenated blood at the same rate, with PGE 1 at the dosage of 25 and 50 ng/kg/min, respectively. The infusion was continuously administered throughout the entire period of ischemia. SESP was measured with epidural electrodes before clamping, 10 and 60 minutes after clamping, and 10 and 60 minutes after declamping. Neurologic outcome was assessed at 24 hours after the operation and graded according to the method of Tarlov. Results: There was no significant hemodynamic change in any group. At 60 minutes after clamping and at 10 and 60 minutes after declamping, the amplitude of SESP was lower than that at preclamping in groups A and B ( p < 0.05). At 60 minutes after clamping and at 10 and 60 minutes after declamping, the SESP was more markedly decreased in group A compared with groups B and C. Regarding postoperative neurologic outcome, the dogs with SESP amplitude of more than 50% of the preclamping control value at 60 minutes after clamping showed neither paralysis nor paraplegia. Seven of nine dogs with less than 50% SESP amplitude showed neurogenic deficit. In a comparison of groups A, B, and C, the Tarlov score for group A dogs was significantly lower than that for group C dogs ( p < 0.05). Conclusion: In this model, PGE 1 administration at the rate of 50 ng/kg/min showed sufficient spinal cord protection against ischemia without a decrease in the blood pressure. Further studies are needed to determine the dose that will provide the maximal protective effect and to determine the maximum duration of ischemia against which PGE 1 shows protective effects. (J Vasc Surg 1998;28:301-7.)

Neurophysiological dysfunction in young women with intractable constipation.

Fifteen women with intractable chronic idiopathic constipation dating from adolescence were investigated by anorectal manometry, neurophysiological evaluation of the conus medullaris and external anal sphincter. Comparison was made with 25 asymptomatic female control subjects. Urological disturbances were common amongst the constipated, in five of whom incidental lumbosacral spinal dysraphism was found. No differences in sphincter pressures or the rectosphincteric reflex were demonstrable between the two groups. Rectal defecatory sensation was blunted and the compliance was increased in the constipated group. The latency of the pudendo-anal reflex was significantly prolonged in idiopathic constipation, two women having an absent reflex (greater than 100 ms). Mean motor unit potential duration of the external anal sphincter was not significantly prolonged in the eight constipated women tested. A central neurogenic deficit is postulated in some women with this disorder.

Constipation in the elderly. A physiologic study.

Colorectal motility was studied in 25 elderly patients with chronic constipation and compared with an asymptomatic control group (N = 17). Proctometrograms were performed to measure rectal volumes at sensory threshold and maximal tolerance, and rectal compliance. Anal sphincter pressures and reflexes were measured by conventional techniques. Indices of colonic motility were also assessed. Significant impairment of rectal sensory threshold was apparent in constipation. Six patients presenting with impaction demonstrated functional megarectums. The remaining 19 showed a significant reduction in maximal rectal volume and rectal compliance and 14 extruded the balloon. There were no differences in sphincter length or presence of the rectosphincteric reflex. Four patients had an absent pudendoanal reflex and the remainder significant prolongation. Total gastrointestinal transit times were prolonged in the constipation group, mainly distally due to rectal stasis. In two patients bisacodyl failed to elicit a sigmoid motor response. Constipation in the elderly is not merely due to delayed transit. Neurogenic deficits of sacral spinal cord function may be responsible for abnormalities in rectal motor and sensory function.

Behavioral Treatment of Ambulatory Function in a Child with Myelomeningocele

Myelomeningocele (spina bifida) is the most common congenital CNS defect. It is characterized by septic distension of the meninges with associated neurogenic deficits and lower extremity paralysis.1 The development of improved medical and surgical techniques has resulted in dramatically increased survival rates in children with myelomeningocele.2 Dietrich reported an 86-percent survival rate out of a total of 500 patients over a 16-year period (S.L. Dietrich, MD, unpublished data, 1979). With such a high survival rate, opportunities now exist for therapists to focus on the habilitation and rehabilitation of children with myelomeningocele.3,4 Recently, biofeedback and nonbiofeedback behavioral techniques have been applied to some of the chronic problems associated with myelomeningocele that are both biological and behavioral in nature and include urinary and fecal incontinence,5–7 obesity,8 deficits in self-help skills,9 and pressure sores.10