Loss Of Pain Sensation Research Articles

Massive Edema of the Lower Limbs in Patients after Spinal Cord Injury—One Picture, Different Diagnoses

Diagnosis of the cause of massive edema of the lower limbs in patients after spinal cord injury (SCI) can be difficult because of loss of pain sensation, commonly occurring in this group of patients. This paper reviews several different pathologies that can lead to lower-limb edema and the associated diagnostic difficulties. We present four cases of patients with massive edemas of lower limbs at different times after SCI undergoing treatment in the Department of Rehabilitation, University Hospital in Bydgoszcz, Poland. All patients had a lack of pain sensation in the lower limbs and significantly elevated levels of D-dimer. In two cases, deep vein thrombosis (DVT) and intramuscular hematomas (IHs) were diagnosed. IHs were probably a consequence of antithrombotic treatments implemented due to the occurrence of DVT. Heterotopic ossification (HO) was diagnosed in a third case, and, in another patient, who was hospitalized for the longest period after injury, we found humeral bone fractures. Heterotopic ossification, intramuscular haematomas, and bone fractures of the lower limb can mimic DVT. Careful observation of the edema evolution is recommended, as the onset of new symptoms may indicate a different cause of edema from that initially established.

Two Case Reports of Hereditary Sensory Autonomic Neuropathy Type IV

Hereditary Sensory Autonomic Neuropathy type IV (HSAN-IV), previously known as congenital insensitivity to pain and anhidrosis (CIPA), is an uncommon condition that presents in infancy with repeated episodes of fever, loss of pain sensations and self-mutilation. We are reporting two patients from two different families. Both patients had history of recurrent fever, anhidrosis, and pain insensitivity and self-mutilation behavior. Both had delayed motor developmental milestones with cognitive impairment. Clinical diagnosis of HSAN type IV was made on the basis of history, clinical examination and excluding other possible causes. Diagnosis of this rare disease is commonly delayed and patients ultimately develop complications. As there is no definitive treatment, these patients and their families should receive proper education and counselling for rehabilitation

Novel Drug Treatments for Diabetes Complications

Diabetes mellitus is a metabolic disease associated with elevated levels of blood glucose. It has become the most prevalent disease in the Saudi population according to the last report from the national prevention program. Diabetes cases can be divided into three types: type I, which requires insulin therapy; type II, which requires the use of hypoglycemic drugs, with or without insulin, and is the most common type in Saudi Arabia; and gestational diabetes, which occurs during pregnancy. We must remember that diabetes can be very dangerous, causing complications in many parts of the body, like the nerves, heart, eyes, and kidneys. According to previous studies, these complications vary depending on the severity of diabetes. They may also affect the blood vessels of the retina, which can develop into diabetic retinopathy. Complications may also be fatal, in the cases of heart attacks, angina, and atherosclerosis. Additionally, they may cause poor circulation that leads to infection and gangrene, or cause neuropathy with numbness and a loss of pain sensations. Diabetic nephropathy is another harmful effect of diabetes that attacks the renal blood vessels. In this article, my aim was to review newly discovered drugs that target and decrease the complications produced by diabetes. My focus here was on certain drugs, including those using nanotechnology, cell-based therapy, angiopoietin like 4, baricitinib, and hepatocyte growth factor (HGF) gene therapy.

Local anaesthetic potential, metabolic profiling, molecular docking and in silico ADME studies of Ocimum forskolei, family Lamiaceae

The present study aimed to detect the bioactive metabolites from Ocimum forskolei aerial parts which are responsible for the local anaesthetic activity of the ethyl acetate fraction. Following a bioassay-guided fractionation, twelve compounds were dereplicated from the ethyl acetate fraction which was the most potent one with a mean onset of action (1.43 ± 0.07****) min compared to tetracaine as a positive control (1.37 ± 0.07****) min. These compounds, along with seven other compounds (isolated by diverse chromatographic techniques) were subjected to a molecular docking study to declare the top scoring compounds predicted to be responsible for such activity. The results highlighted Rabdosiin and Apigenin-7-O-rutinoside as the main bioactive leaders of the local anaesthesia via forming multiple H- bonding with the sodium ion channels leading to their blockade and loss of pain sensation, which strongly supports the use of O. forskolei as a local anaesthetic agent.

Primary stabilisation for tail avulsion in 15 cats

To evaluate the effects of a primary tail stabilisation technique in relieving pain and supporting nerve recovery in cats that have lost voluntary motor function and pain sensation in the tail without caudal nerve transection. Retrospective review of medical records and preoperative diagnostic tests, including clinical examination results and tail radiographs of cats suffering from tail avulsion with loss of pain perception in the tail between 2009 and 2015. Cats with open tail fracture, tail wounds that necessitated an amputation or caudal nerve root transection were excluded. Tail reconstruction was performed, after surgical exploration, with two nylon sutures. Fifteen cats were included, all of which had lost voluntary motor function in the tail and 8 of 15 were urinary incontinent. After surgery, 11 cats recovered voluntary tail function and pain sensation within 14 to 90 days (mean 39 days). Five of the eight previously incontinent cats recovered urinary continence within a month of surgery. The reported method of primary tail stabilisation is associated with recovery of lost function in the majority of cats presenting with tail avulsions, loss of pain sensation in the tail but without caudal nerve root transection. A comparison study is required to determine whether these results are superior to conservative management.

Effects of different doses of dexmedetomidine on median effective concentration of ropivacaine for brachial plexus block

Objective To determine the optimum dose of dexmedetomidine administered locally through evaluating the effects of different doses of dexmedetomidine on the median effective concentration(EC50)of ropivacaine for brachial plexus block. Methods American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes, aged 19-50 yr, weighing 50-80 kg, scheduled for elective ulna and radius fracture open reduction and internal fixation, requiring ultrasound-guided axillary brachial plexus block, were randomly assigned into 4 groups using a random number table: control group(group C)and dexmedetomidine 0.4, 0.6 and 0.8 μg/kg groups(D1, D2 and D3 groups). Axillary brachial plexus block was performed only with ropivacaine in group C. In D1-3 groups, axillary brachial plexus block was performed with the mixture of ropivacaine and dexmedetomidine 0.4, 0.6 and 0.8 μg/kg, respectively.The effective block was defined as complete loss of pain sensation in the areas innervated by the brachial plexus.The volume of local anesthetics was 40 ml.The concentration of ropivacaine was determined by up-and-down technique.The initial concentration was 0.4% and the ratio between the two successive concentrations was 1.0.If the block was effective, the next patient received a lower dose of ropivacaine; or conversely if ineffective, a higher dose was given in the next patient.At least 7 independent crossover pairs were observed in each group.The EC50 of ropivacaine was the mean of the concentration of ropivacaine of each crossover pair.The occurrence of brachial plexus block-related adverse events, adverse cardiovascular events and over-sedation was recorded. Results In C, D1, D2 and D3 groups, 20, 22, 24 and 19 patients were enrolled, respectively.Compared with group C, the EC50 of ropivacaine was significantly decreased in D2 and D3 groups, and no significant change in the EC50 of ropivacaine was found in group D1.No patients developed adverse events in group D1.The incidence of bradycardia was 17%, but it was transient in group D2.In group D3, the incidence of bradycardia and hypotension was 58% and 32%, respectively, and they required special treatment, and the incidence of over-sedation was 10%. Conclusion The optimum dose of dexmedetomidine is 0.6 μg/kg when mixed with ropivacaine for brachial plexus block. Key words: Dexmedetomidine; Amides; Brachial plexus; Nerve block; Dose-response relation, drug

Effect of local application of dexmedetomidine on the medium effective concentration of ropivacaine for brachial plexus block

Objective To investigate effect of local application of dexmedetomidine on the medium effective concentration (EC50) of ropivacaine for brachial plexus block and the mechanism of the analgesic effect induced by dexmedetomidine.Methods Fifty-two ASA Ⅰ or Ⅱ patients of both sexes,aged 18-50 yr,weighing 50-80 kg,scheduled for elective forearm or hand surgery,requiring ultrasound-guided axillary brachial plexus block,were randomly assigned into 2 groups (n =26 each):control group (group C) and dexmedetomidine group (group D).Axillary brachial plexus block was performed using only ropivacaine in group C.In group D the mixture of ropivacaine and 0.8 μg/kg dexmedetomidine was injected for the block.The effective block was defined as complete loss of pain sensation in the brachial plexus distribution.The volume of local anesthetics was 30 ml.The concentration of ropivacaine was determined by up-and-down technique.The initial concentration was 0.5 ％ and the ratio between the two successive concentrations was 1.2.If the block was effective,the next patient received a lower dose of ropivacaine,or if ineffective,a higher dose was given in the next patient.The EC50 and 95 ％ confidence interval of ropivacaine were determined using the Dixon-Massey method.Results The EC50 (95 ％ confidence interval) of ropivacaine was 0.32％ (0.30％-0.33％) in group D and 0.44％ (0.42％-0.46％) in group C.The EC50 of ropivacaine was significantly lower in group D than in group C (P ＜ 0.05).Conclusion Local application of dexmedetomidine can decrease the EC50 of ropivacaine for brachial plexus block guided by ultrasound,indicating that the mechanism of the analgesic effect induced by dexmedetomidine is related to the local anesthetic-like effect. Key words: Dexmedetomidine ; Amides ; Brachial plexus ; Nerve block ; Dose-response relationship, drug

Epidemiology of hereditary sensory and autonomic neuropathy type IV and V in Japan

Hereditary sensory and autonomic neuropathy (HASN) refers to a group of rare congenital disorders characterized by loss of pain sensation and other sensory or autonomic abnormalities. Among them, a relatively large proportion of patients with HSAN type IV, which is accompanied by anhidrosis and intellectual disability, are reported from Israel and Japan. HSAN type V, with normal sweating and mental development, is rarely reported in Japan. In 2009, we founded a research group for congenital insensitivity to pain and performed the first epidemiological survey of HSAN types IV and V in Japan. Questionnaires were sent to a total of 3,488 certified training institutions of five nationwide medical societies comprising pediatricians, neurologists, orthopedic surgeons, and dentists. Answers were obtained from 1,610 institutions, and 192 HSAN patients (152 with type IV and 28 with type V) were reported from 105 institutions. After excluding duplicated patients, we identified a total of 62 current, 36 past, and five deceased patients for HSAN-IV, and a total of 14 current, 13 past, and 0 deceased patients for HSAN-V. Using these figures, we estimated that the number of Japanese patients with HSAN types IV and V as 130-210 and 30-60 patients, respectively. We identified no gender differences, and patients with a family history of the disorder were limited to affected siblings in both conditions. Most patients with HSAN-IV were 5-40 years of age, whereas half of the patients with HSAN-V were 40 years or older.

Autotransplanting of Bone Marrow-Derived Mononuclear Cells for Complete Cases of Canine Paraplegia and Loss of Pain Perception, Secondary to Intervertebral Disc Herniation

Severe intervertebral disc herniation causes complete paraplegia and loss of pain sensation in canines. The prognosis is poor, even when decompression surgery is performed immediately after onset. Studies suggest that bone marrow-derived mononuclear cells will regenerate the injured spinal cord and restore neurologic function. This study was conducted to assess the clinical efficacy of bone marrow-derived mononuclear cell autotransplanting in severe cases of canine intervertebral disc herniation. Eighty-two dogs (miniature dachshunds) with severe thoracolumbar intervertebral disc herniation were used. All had intervertebral disc herniation accompanied by paraplegia and loss of pain perception. In 36 dogs, bone marrow-derived mononuclear cells were autotransplanted to the lesioned spinal cord immediately after decompression surgery. Bone marrow was collected from the proximal humerus and subjected to density gradient centrifugation to isolate the bone marrow-derived mononuclear cells. The remaining 46 dogs (receiving surgical treatment only) were assigned as controls. Therapeutic efficacy was compared based on the rate of ambulatory recovery. Ambulatory recovery was observed in 88.9% and 56.5% of animals in the bone marrow-derived mononuclear cells and control groups, and a significant difference was found. No complications were found in bone marrow-derived mononuclear cells group. Bone marrow-derived mononuclear cell transplanting revealed a significant increase in the recovery rate and, as has been reported in rats and humans, bone marrow-derived mononuclear cell autotransplanting shows efficacy in canines as well.

The great pretender

In November, 2009, a 40-year-old man presented to us because of diffi culty in walking, facial asymmetry, and numbness in both legs. His symptoms had begun 6 weeks earlier with a sensation of pins and needles in both thighs spreading distally. At the same time he noticed a left facial droop, with involvement of the right side soon after. There was no change in bladder or bowel function. He had diabetes mellitus and was receiving insulin. He had no history of signifi cant exposure to toxins or alcohol misuse. There was no family history of neurological problems. He had recently been found HIV negative on testing after starting a new heterosexual relationship and reported no symptoms of sexually transmitted infections. Physical examination showed no rash or lymphadenopathy. His left conjunctiva was injected; both pupils reacted normally. On neuro logical examination he had bilateral lower motor neuron facial weakness and mild proximal leg weakness with 4– power in hip fl exion, 4+ at the knees, with full power elsewhere. Tone was normal but refl exes were globally absent with fl exor plantar responses. There was no muscle wasting or fasciculations. Loss of pain sensation was elicited in both legs in a high stocking distribution extending to the upper thigh. Position sense was intact. A clinical assessment of subacute sensorimotor polyneuropathy was made, and the diagnosis of GuillainBarre syndrome was considered. Although diabetes can present with chronic predominantly sensory peripheral neuropathy, cranial mononeuropathy, and radiculoplexus neuropathy, we thought the last less likely in view of the bilateral facial weakness and the absence of pain. Cerebrospinal fl uid (CSF) analysis showed a high protein concentration and lymphocyte count (fi gure). Because Guillain-Barre syndrome is rarely associated with CSF pleiocytosis in immunocompetent patients, we did a VDRL test on CSF; the result was positive, as was that for serum (titre 1 to 128), confi rming an unexpected diagnosis of neuro syphilis. Our patient was treated with intravenous benzyl penicillin 5 mU every 6 h. After 14 days of treatment his sensory symptoms had resolved, and within a month after discharge he had regained full power, including of the facial muscles. At fi nal follow-up in November, 2010, a repeat HIV ELISA was negative and he had made a full recovery. He had disclosed the diagnosis to his sexual partner who underwent screening and treatment. Neurosyphilis can be divided into early and late forms. In our patient, a cellular response in the CSF, rapid symptom onset, and strongly positive serum VDRL favoured early disease with meningeal involvement. Late neurosyphilis manifests as tabes dorsalis and syphilitic paresis resulting from brain and cord parenchymal infection. There is evidence that the clinical spectrum of neurosyphilis has changed in the post-antibiotic era, with early forms now predominating. Diagnosis of neuro syphilis can be challenging and requires a combination of tests. Although CSF-FTA assays are reactive in more cases than the CSF-VRDL in all stages of syphilis, their specifi cities are less well established and they are not regarded as a valid basis for the diagnosis of neurosyphilis in isolation. By contrast, VDRL is highly specifi c in the CSF and is regarded as the standard serological test, but it reportedly has lower sensitivity. Immunocompetent patients with positive serum treponemal tests and compatible clinical signs should be treated for neurosyphilis if the CSF shows a raised protein concentration or leucocyte count. Syphilis is a great mimicker in clinical medicine, and neurosyphilis can occur early after infection, in many cases without accompanying peripheral manifestations. The diagnosis should be considered in patients presenting with symptoms and signs resembling Guillain-Barre syndrome and CSF pleiocytosis.

Altered pain perception in schizophrenia

In June, 2009, a 51-year-old woman presented with a 4-day history of abdominal swelling and fever, and a 2-week history of loss of appetite. There was no history of abdominal pain or nausea. She was febrile (38·4°C) and her abdomen was swollen but soft without spontaneous pain or tenderness. She had a history of schizophrenia since the age of 40 years which was well controlled with perospirone 12 mg/day and quetiapine 150 mg/day. At the age of 45 years, she was diagnosed with diabetes mellitus and had achieved good glycaemic control (HbA1c 6·5%) with biphasic insulin aspart 30 (6 U/day). There was no sign of obvious peripheral neuropathy. Laboratory test results showed normocytic anaemia (haemoglobin 95 g/L), leucocytosis (13·3×109/L) with neutrophilia (91·5%), high concentration of C-reactive protein (129 mg/L), and normal liver and kidney function. Urinalysis showed negative protein and no leucocytosis. Chest radiography showed normal lungs with no cardiac enlargement. Abdominal CT showed a large volume of partly encapsulated ascites (fi gure). The peritoneum in her pelvic cavity was thickened, and ascites in the right inferior abdominal cavity contained calcifi cation and air (fi gure). The aspirated ascitic fl uid had an unpleasant smell and was suppurated. Culture of the fl uid was positive for pyogenic agents, including Peptostreptococcus spp and Bacillus subtilis. Blood culture was negative. We diagnosed severe bacterial pan-peritonitis. Surprisingly, her general condition was stable and she did not complain of any abdominal pain. Abdominal drainage was done and antibiotics started (imipenem/ cilastatin 1·5 g/day), but her symptoms did not improve. Therefore, laparotomy was done on the seventh day of admission. On laparotomy, a large amount of yellowish, turbid, gel-like material fi lled the abdominal cavity with retention of pus in the pouch of Douglas. The appendix was necrotic and contained faecolith. The bacterial peritonitis was suspected to be caused by perforation associated with acute appendicitis. Postoperative course was uneventful, and the patient recovered. When last seen in October, 2009, the patient was well. Even though our patient had a purulent pan-peritonitis caused by a perforated appendix, she did not present with abdominal pain, tenderness, or guarding. Diminished pain sensitivity or loss of pain sensation in people with schizophrenia has previously been reported in cases of acute myocardial infarction and perforated gastrointestinal tract. Clinically, diminished pain sensitivity in schizophrenia has been linked to key features of the disorder, such as positive symptoms, aff ective fl attening, or attention defi cits. Disturbances in dopamine, serotonin, glutamate, and opioids have been proposed to account for hypoalgesia in schizophrenia. Hypoalgesia in schizophrenia has been reported throughout the acute phase of illnesses and in medicated stable or drug-free patients; neuroleptic drugs have been suggested to have minor analgesic eff ects. Diabetes occurs in people with schizophrenia two to four times more often than in the general population. Compared with people without diabetes, appendicitis in people with diabetes is more likely to result in perforation or other complications. Decreased pain sensation may result in aggravation of the condition and in a delay of diagnosis and treatment. Our case is an important reminder that people with schizophrenia do not always present with typical clinical features of acute abdominal disease pathology.

TANINIZ NEDİR?

A 36-year-old woman presented with an unusual deformity in her hands that began ten years ago. She noticed thermal sensory loss in her hands. On examination, her fingers were thickened, nails deformed, and there were slowly healing ulcers and fissures in her palms (Figure 1). On neurological examination, there was touch, thermal and pain sensory loss limited to her arms. The cranial nerves were normal. Tendon reflexes were normal in the arms, and exaggerated in the legs. Hoffmann and Babinski signs were elicited bilaterally.

The identification and characterization of Glucagon‐like Peptide‐1 receptors on rat peripheral nerves

Peripheral neuropathy, a common neurological disorder and a major cause of neuropathic pain, results in negative symptoms such as thermal hypoalgesia, loss of pain sensation, undetected infections and limb amputations, and positive symptoms such as burning and stabbing pain. The well established sciatic nerve injury model exhibits an equivalent capacity of regeneration in rats compared to subhuman primates. Glucagon‐like peptide 1 (GLP‐1), an incretin hormone secreted from the enteroendocrine L cells in distal ileum and colon, increases circulating postprandial insulin levels. While it has been reported that GLP‐1 exhibits neuroprotection, no studies have yet been undertaken to identify GLP‐1 receptors on peripheral nerves. Therefore, it is unknown whether GLP‐1's beneficial effects are through a direct action on the nerves or indirectly through elevated insulin levels. We performed immunoblotting assays using a rabbit polyclonal antibody to the GLP‐1 receptor. A 34kDa protein band was detected in homogenates of rat peripheral sciatic nerves and rat insulinoma RINm5F cells known to express the GLP‐1 receptor. Future studies will characterize GLP‐1 receptors on sciatic nerve and evaluate the effects of GLP‐1 on neurobehavioral aspects of neuropathy caused by neurotrauma and conditions like diabetes. These findings may aid in the development of potential therapies for peripheral neuropathy.

Lack of pain in schizophrenia: a patient whose arm was burned and amputated

Diminished pain sensitivity or loss of pain sensation in schizophrenic patients has previously been reported. We report an interesting case of a schizophrenia patient who had the disease for 20 years and who had his forearm amputated below the elbow level due to severe burn injury to his muscles, tendons, nerve fibers and bone tissue, caused by direct exposure to flames from a liquefied petroleum gas cylinder, in an attempt to make himself warm during a medicine-free period with active symptoms and without pain sensation.

Ischemic Preconditioning Prevents Skeletal Muscle Tissue Injury, But Not Nerve Lesion Upon Tourniquet-Induced Ischemia

Prolonged ischemia followed by reperfusion (I/R) of skeletal muscle results in significant tissue injury. Ischemic preconditioning (IPC), achieved by brief periods of ischemia before sustained ischemia, has been shown to ameliorate I/R injury in a variety of tissues. We demonstrate that tourniquet hind limb ischemia-induced injury of the muscle benefits from IPC, whereas the peripheral nerve suffers from prolonged ischemia time and mechanical deterioration on IPC. In anesthetized rats, hind limb ischemia was induced by tourniquet for 3 hours followed by 24 hours of reperfusion. In an additional series of experiments, IPC (three cycles of 10 minutes I/10 minutes R) preceded hind limb ischemia. Sham-operated animals without ischemia served as controls. Skeletal muscle tissue injury was assessed with respect to microcirculation, inflammatory cell response, and cell integrity using intravital fluorescence microscopy, Western blot protein analysis, and tissue histochemistry. Analysis of tactile and thermal allodynia served as indicators for postischemic pain. In addition, motor nerve conduction velocity and transmission electron microscopy allowed assessing postischemic nerve lesion. Tourniquet of the hind limb caused marked perfusion failure, enhanced leukocyte-endothelial cell interaction, and apoptotic cell death. IPC was able to improve microvascular perfusion and to reduce inflammatory cell response. Of interest, apoptotic cell death, assessed by cell nuclear morphology in vivo as well as Western blot and immunohistochemical analysis of caspase-3 cleavage, can be substantially reduced by IPC in tourniquet ischemia of the hind limb. Application of the tourniquet abolished nerve conduction in all animals. Non-IPC-treated animals still showed tactile allodynia, whereas IPC further caused loss of pain sensation and motor function of the postischemic hind limb. High susceptibility of the peripheral nerve to compression-induced ischemic injury disproves IPC in its clinical application for surgical procedures requiring prolonged tourniquet ischemia.

Foot problems in diabetes: an overview.

Diabetes is the leading cause of nontraumatic lower-extremity amputations in the United States. Most amputations are preceded by an ulcer, and ulcers are costly in their own right. Most ulcers are neuropathic in etiology and plantar in location. They occur typically at sites of high mechanical loading because of repetitive trauma in people with loss of pain sensation. In an adequately perfused limb, such ulcers are not difficult to heal. When they are properly mechanically off-loaded, approximately 90% of these wounds heal in approximately 6 weeks. The reference standard off-loading device is the total contact cast, but other reasonably efficacious methods exist. Screening and implementation of preventive measures in the high-risk patient are highly recommended and can reduce the incidence of ulceration. All patients with diabetes should be screened annually for loss of protective sensation, with the 10-g Semmes-Weinstein monofilament being the easiest tool to use. Education to prevent complications should be implemented for all patients with loss of protective sensation.

Episodic pain associated with a tumor in the parietal operculum: a case report and literature review

We report a young woman suffering brief painful episodes in her right arm which sometimes spread to the whole right side of her body. The episodes were initially rare, but over 13 months they became increasingly frequent until occurring every 20 min. Neurological examination was normal. Magnetic resonance imaging revealed a lesion in the white matter of the parietal operculum. Lesions in the parietal operculum associated with persisting thalamic pain or loss of pain sensation have been reported, but rarely with episodic pain. Since episodic painful attacks have been described in association with various suprathalamic lesions, we conclude that paroxysmal pain attacks may be another consequence of the disturbance of the normal pattern of thalamocortical connections to the second sensory cortical area by a lesion, in our case, of the subcortical area of the parietal operculum.

Exclusion of p75 NGFR and other candidate genes in a family with hereditary sensory neuropathy Type II

Hereditary sensory neuropathy Type II (HSN II) is an autosomal recessive disorder characterized by the loss of peripheral sensory modalities in individuals with otherwise normal development. Patients with HSN II often have chronic ulceration of the fingers and toes, autoamputation of the distal phalanges, and neuropathic joint degeneration associated with loss of pain sensation. Recent descriptions of a similar phenotype in mice carrying a targeted mutation in the low affinity nerve growth factor receptor, p75 NGFR, suggested the possibility that mutations in this gene or other members of the nerve growth factor (NGF) family of genes and their receptors might be responsible for this human disorder. In this study candidate genes were evaluated by their inheritance pattern in two sisters affected with HSN II, their unaffected sister and mother in a consanguineous family. The segregation of polymorphic alleles at and around loci for p75 NGFR, TRKA, TRKB, BDNF, and familial dysautonomia (another hereditary sensory neuropathy having features in common with HSN II) virtually excluded these genes as the cause of HSN II in this family. Further evaluation of loci for other neurotrophic factors and their receptors, which will be possible when mapping information on their loci becomes available, may permit the identification of the gene responsible for HSN II.

T Cell–mediated ganglionitis associated with acute sensory neuronopathy

A 67-year-old man presented with acute painful sensory loss, areflexia, ataxia, urinary retention, and severe constipation and became unable to walk within 2 weeks. He died suddenly 5 weeks after the onset of symptoms. Autopsy revealed widespread inflammation of sensory and autonomic ganglia with immunocytochemical evidence of a CD8+ T cell-mediated cytotoxic attack against ganglion neurons. This observation suggests a novel pathogenetic mechanism of immune-mediated human ganglion cell damage comparable to mechanisms operating in polymyositis.

Evidence for segregated pain and temperature conduction within the spinothalamic tract

The lateral spinothalamic tract, located in the anterolateral quadrant of the white matter of the spinal cord, is one of the most important structures in transmitting pain within the central nervous system. It has been known for almost a century that destruction of fibers in this tract results in analgesia contralateral to the lesion. The effectiveness and clinical importance of interruption of the lateral spinothalamic tract has been proven in many studies. Today cordotomies are still a useful neurosurgical treatment modality, especially when pain can no longer be sufficiently controlled by analgesic drugs. Although analgesia on the contralateral side is the desired effect, one must also expect to cause disturbance in temperature sensation when performing a cordotomy. The authors' observations showed that after a cordotomy the dermatome level of analgesia can be variable within certain limits, which is in accordance with the literature. Surprisingly, however, the loss of temperature sensation may differ significantly from the loss of pain sensation. It was also found to be possible to perform a successful cordotomy without altering the sensation of temperature at all. This indicates that pain and temperature sensations may be conducted via separate pathways. Possible mechanisms underlying this phenomenon are discussed.