Does Beta Thalassemia Increase the Incidence of Bell＇s Palsy？

A five-year old Iraqi patient with beta thalassemia major was presented with recurrent attack of Bell＇s palsy on 2 successive years being a milder one in the second year. This is a rare occurrence in beta thalassemia major patients and needs to be further explored. This is a case report of a nine-year old Iraqi child who is the only child born to parents of secondary consanguinity relatives from Babil Province who was diagnosed as beta thalassemia on the age of 6 months and is on regular blood transfusion and iron chelation therapy of deferasirox tablets （Exjade）, his medical follow up takes place at Babil Thalassemia center in Babil Maternity and Child Hospital. On the age of five years, he was presented with a sudden onset of right sided Bell＇s palsy within twenty four hours of swimming in a cool swimming pool at his home in July 2011. A neurosurgeon examined him at that time, no investigations were done, the diagnosis was purely clinical, steroid ＆ neurotonics were recommended as a treatment for the condition, antiviral agents were not prescribed, lacrimation ＆ taste were not affected, there was a slow improvement, two weeks later physiotherapy sessions including facial massage ad electric stimulation were recommended after which the child improved. The next year, another attach of Bell＇s Palsy developed at a similar time with the same sequel of events, this time the attack was milder and with residual effects seen in the eye ＆ mouth. This coincidence of beta thalassemia and Bell＇s palsy should be further studied by observational epidemiologic studies to prove or disprove the hypothesis that thalassemic patients especially children are at higher risk of developing Bell＇s palsy than healthy children. Beta thalassemia patients may be at higher risk of developing Bell＇s Palsy.

Metaphysical Energy Therapy in the Treatment of Cranial Nerve Palsies with Special Reference to Bell’s Palsy

Neuropathy, or nerve injury, is a severe and common impediment of diabetes. Studies evaluate that 50% of people with diabetes will develop neuropathy. Diabetic nerve injury is impairment of a single solitary nerve (also named mononeuropathy). Com- monly 2 cranial nerves Viz., cranial nerve VII and cranial nerve VI are involved in facial nerve palsies. The former one is called Bell’s palsy and is acute Lower Motor Neuron facial nerve paralysis (>80%) causing an inability to control facial muscles on the affected side. The later one is sixth nerve palsy, (the abducens nerve), which is responsible for triggering contraction of the lateral rectus muscle to abduct (i.e., turn out) the eye resulting in double vision on the affected side. In recent times, we have found to our amazement, rapid restoration of normalcy within a few hours to a few days, of Cranial Nerve palsies in diabetic subjects at our centre. We are presenting a group of cases having Type2DM over different time periods from 6 to 20 years and those who suddenly suffered facial nerve palsy and they came to VHSDRC for treatment. They were started on the new modality called the Dynamic Acupuncture Mediated Meta-physical Energy Therapy (DAMM Therapy), to recover from the facial palsy. The DAMM therapy is a unique novel way of infusing and transferring healing energy from the therapist to the patient. Within 2 - 7 sittings of DAMM therapy patients showed 75% - 100% improvement in their clinical condition.

Needle Sensation and Personality Factors Influence Therapeutic Effect of Acupuncture for Treating Bell＇s Palsy： A Secondary Analysis of a Multicenter Randomized Controlled Trial

Background： It has not been solved what kind of needle sensation might influence outcomes of acupuncture treatment. Effects of personality factors on the therapeutic effect of acupuncture have not been investigated. This study aimed to find the effects of the traits of personality on the objective outcome when different acupuncture techniques were used in treating patients with Bell＇s palsy. Methods： We performed a secondary analysis of a prospective multicenter randomized controlled trial of acupuncture for Bell＇s palsy. Patients were randomly assigned to the de qi and control groups, respectively. The primary outcome was facial nerve function at month 6. The intensity of each needle sensation was rated by a visual analog scale. Psychosocial thctors were assessed by the pretreatment mediator questionnaire： 16 Personality Factor Questionnaire （16PF） was used tbr assessing personality factors and digit cancellation test for assessing attention. Results： After 6 months, patients in the de qi group had better facial function （adjusted odds ratio [OR]： 4.16, 95% confidence interval [CI]： 2.23-7.78）. Path analysis showed that intensity of needle sensation of fullness had direct effect on House-Brackmann （HB） score at month 6. In de qi group, the low HB score on day I （OR： 0.13, 95% （_7： 0.03-0.45） and the low Social Boldness score （OR： 0.63, 95% CI： 0.41-0.97） in 16PF were associated with better facial function. In control group, low HB score on day 1 （OR： 0.25, 95% CI： 0.13-0.50）, low Vigilance score （OR： 0.66, 95% CI： 0.50-0.88）, and high Tension score （OR： 1.41,95% CI： 1.12 1.77） in 16PF were related to better facial function. Conclusions： The needle sensation of fullness could predict better facial function and personality traits might influence outcomes of acupuncture treatment. Both of them should be considered seriously in acupuncture treatment and research.

Acupuncture and vitamin B_(12) injection for Bell's palsy:no high-quality evidence exists

OBJECTIVE： To assess the efficacy of acupuncture combined with vitamin B12 acupoint injection versus acupuncture alone to reduce incomplete recovery in patients with Bell＇s palsy. DATA RETRIEVAL： A computer-based online retrieval of Medline, Web of Science, CNKI, CBM databases until April 2014 was performed for relevant trials, using the key words ＂Bell＇s palsy or idiopathic facial palsy or facial palsy＂ and＂acupuncture or vitamin B12 or methylcobalamin＂. STUDY SELECTION： All randomized controlled trials that compared acupuncture with acupuncture combined with vitamin B12 in patients with Bell＇s palsy were included in the me- ta-analysis. The initial treatment lasted for at least 4 weeks. The outcomes of incomplete facial recovery were monitored. The scoring index varied and the definition of healing was consistent. The combined effect size was calculated by using relative risk （RR） with 95% confidence interval （C/） using the fixed effect model of Review Manager. MAIN OUTCOME MEASURES： Incomplete recovery rates were chosen as the primary outcome. RESULTS： Five studies involving 344 patients were included in the final analysis. Results showed that the incomplete recovery rate of Bell＇s palsy patients was 44.50% in the acupuncture combined with vitamin B12 group but 62.57% in the acupuncture alone group. The major acupoints were Taiyang （EX-HN5）, Jiache （ST6）, Dicang （ST4） and Sibai （ST2）. The combined effect size showed that acupuncture combined with vitamin B12 was better than acupuncture alone for the treatment of Belrs palsy （RR = 0.71, 95%CI： 0.58-0.87; P = 0.001）, this result held true when 8 patients lost to follow up in one study were included into the analyses （RR = 0.70, 95%CI： 0.58-0.86; P = 0.0005）. In the subgroup analyses, the therapeutic effect in patients of the electroacupuncture subgroup was better than in the non-electroacupuncture subgroup （P = 0.024）. There was no significant dif- ference in the incomplete recovery rate by subgroup analysis on drug types and treatment period. Most of the included studies were moderate or low quality, and bias existed. CONCLUSION： In patients with Bell＇s palsy, acupuncture combined with vitamin 812 can reduce the risk of incomplete recovery compared with acupuncture alone in our meta-analysis. Because of study bias and methodological limitations, this conclusion is uncertain and the clinical appli- cation of acupuncture combined with vitamin B12 requires further exploration.

Bell’s palsy and choreiform movements during peginterferon α and ribavirin therapy

Neuropsychiatric side effects of long-term recombinant interferon-α therapy consist of a large spectrum of symptoms. In the literature, cranial neuropathy, especially Bell's palsy, and movement disorders, have been reported much less often than other neurotoxic effects. We report a case of Bell's palsy in a patient with chronic hepatitis C during peginterferon-α and ribavirin therapy. The patient subsequently developed clinically inapparent facial nerve involvement on the contralateral side and showed an increase in choreic movements related to Huntington's disease during treatment.

Allogeneic mesenchymal stem cells may be a viable treatment modality in cerebral palsy

BACKGROUND Cerebral palsy(CP)describes a group of disorders affecting movement,balance,and posture.Disturbances in motor functions constitute the main body of CP symptoms.These symptoms surface in early childhood and patients are affected for the rest of their lives.Currently,treatment involves various pharmacotherapies for different types of CP,including antiepileptics for epilepsy and Botox A for focal spasticity.However,none of these methods can provide full symptom relief.This has prompted researchers to look for new treatment modalities,one of which is mesenchymal stem cell therapy(MSCT).Despite being a promising tool and offering a wide array of possibilities,mesenchymal stem cells(MSCs)still need to be investigated for their efficacy and safety.AIM To analyze the efficacy and safety of MSCT in CP patients.METHODS Our sample consists of four CP patients who cannot stand or walk without external support.All of these cases received allogeneic MSCT six times as 1×106/kg intrathecally,intravenously,and intramuscularly using umbilical cord-derived MSCs(UC-MSC).We monitored and assessed the patients pre-and post-treatment using the Wee Functional Independence Measure(WeeFIM),Gross Motor Function Classification System(GMFCS),and Manual Ability Classification Scale(MACS)instruments.We utilized the Modified Ashworth Scale(MAS)to measure spasticity.RESULTS We found significant improvements in MAS scores after the intervention on both sides.Two months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;four months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;12 months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046.However,there was no significant difference in motor functions based on WeeFIM results(P>0.05).GMFCS and MACS scores differed significantly at 12 months after the intervention(P=0.046,P=0.046).Finally,there was no significant change in cognitive functions(P>0.05).CONCLUSION In light of our findings,we believe that UC-MSC therapy has a positive effect on spasticity,and it partially improves motor functions.

Infrared thermography and meridian-effect evidence and explanation in Bell's palsy patients treated by moxibustion at the Hegu (LI4) acupoint Overall regulation or a specific target?

Subjects with Bell＇s palsy and healthy individuals were treated with moxibustion thermal stimulation on the Hegu （LI4） acupoint; an infrared thermal imaging system was used to observe facial-temperature changes. Bell＇s palsy patients developed low or high temperatures at the affected side, with poor symmetry. Healthy people showed high temperatures on the forehead, medial angle of the eye, nasal ala and around the lips, but low temperatures on bilateral cheeks, thus forming a ＂T-type hot area＂ in the face, with good temperature symmetry. Moxibustion treatment for 11 minutes significantly improved high asymmetry in temperature in the faces of Bell＇s palsy patients. This evidence indicates that moxibustion treatment on Hegu enables increases in facial temperatures in healthy people and Bell＇s palsy patients, especially around the lips. Moxibustion stimulation at the Hegu not only improves the global circulation but also has specific effects on the lips in Bell＇s palsy patients, but the underlying mechanism needs further investigation.

Psychological Factors Are Closely Associated with the Bell's Palsy: A Case-control Study

To observe the differences in psychological status between Bell’s palsy (BP) patients and healthy subjects, and to examine the relationship between psychological factors and the severity of BP, we conducted a case-control, multi-center clinical investigation. A total of 695 subjects were assigned to the case group (n=355) and the control group (n=340). House–Brackmann grading system and Facial Disability Index (FDI) were adopted to assess the BP patients; Kessler Psychological Distress Scale (K10) and 16 Personality Factor (16PF) scale were employed to evaluate the psychological distress and personality profiles of all subjects. Two independent samples t test was used to compare the differences between cases and controls, and to compare the differences among different BP patients. Pearson correlation analysis was used to examine the relationship between psychological factors and severity of facial paralysis. The results showed that psychological distress (K10) in case group (27.09±5.80) was significantly higher than that in control group (13.43±3.02) (t=–37.219, P=0.000). The scores of personality factor Warmth (A), Openness to Change (Q1), Self-Reliance (Q2) were lower in cases than in the controls (P<0.01, P<0.05, P<0.05, respectively), whereas the scores of Sensitivity (I), Vigilance (L), Apprehension (O), and Tension (Q4) were significantly higher in cases than in the controls (P<0.05, P<0.01, P<0.01, P<0.01, respectively). In addition, the psychological distress was significantly higher in female patients, severe (HB score Ⅳ–Ⅵ) patients, and subacute (onset time 72–168 h) patients compared with that in male patients, mild (HB score Ⅰ–Ⅲ)patients, and acute (onset time≤72 h) patients (P<0.05). The scores of personality factor in female patients, severe patients, and subacute patients were also significantly different from male patients, mild patients, and acute patients (P<0.05). The result of Pearson correlation analysis showed that psychological factors (K10, personality A, F, L, N, O, Q4) were closely related to HB scores. We are led to conclude that the psychological status between BP patients and healthy people are different; psychological distress and personality factors are closely associated with severity of facial paralysis.

Bell’s palsy workup:Does audiometry add value?

Objective:To investigate if routine audiometry in Bell’s palsy patients has prognostic value.Methods:Retrospective case review was conducted on all Bell’s palsy patients(n紏191)seen at the tertiary otolaryngology specialist outpatient clinic from 2015 to 2017.Correlation of ipsilesional audiometric thresholds with patients’time-to-recovery and initial clinical severity(measured by House-Brackmann(HB)scoring)were used for the prognostic outcome measure.Audiometry results were analyzed using three contiguous frequency pure-tone average(1kHz,2kHz,4kHz).Statistical analysis was done via Stata(v13.1),significance tests were 2-sided at 5%significance level.Results:There was no significant difference between audiometric thresholds between the ipsilesional ear and the contralateral ear(p=0.87).Time-to-recovery was significantly longer for patients with severe initial presentation as compared to mild and moderate severity(p<0.01).There was no correlation found between the audiometry results and HB score at presentation(p=0.39).There was no correlation found between ipsilesional audiometric thresholds and time-to-recovery(p=0.58).Conclusion:Our study suggests that routine audiometry has limited prognostic value in Bell’s palsy patients.

Fermions: Spin, Hidden Variables, Violation of Bell’s Inequality and Quantum Entanglement

Using real fields instead of complex ones, it was recently claimed, that all fermions are made of pairs of coupled fields (strings) with an internal tension related to mutual attraction forces, related to Planck’s constant. Quantum mechanics is described with real fields and real operators. Schrodinger and Dirac equations then are solved. The solution to Dirac equation gives four, real, 2-vectors solutions ψ1=(U1D1)ψ2=(U2D2)ψ3=(U3D3)ψ4=(U4D4)where (ψ1,ψ4) are coupled via linear combinations to yield spin-up and spin-down fermions. Likewise, (ψ2,ψ3) are coupled via linear combinations to represent spin-up and spin-down anti-fermions. For an incoming entangled pair of fermions, the combined solution is Ψin=c1ψ1+c4ψ4where c1and c4are some hidden variables. By applying a magnetic field in +Z and +x the theoretical results of a triple Stern-Gerlach experiment are predicted correctly. Then, by repeating Bell’s and Mermin Gedanken experiment with three magnetic filters σθ, at three different inclination angles θ, the violation of Bell’s inequality is proven. It is shown that all fermions are in a mixed state of spins and the ratio between spin-up to spin-down depends on the hidden variables.

Isolated Bell's palsy-An unusual presentation of dengue infection

Dengue fever is a very common arthropod-borne infection in tropical countries.Neurological complications in dengue fever are relatively uncommon and among these,isolated cranial neuropathies have been reported only very rarely.We present an unusual neurological complication of Bell’s palsy(lower motor neuron 7 th nerve palsy) associated with dengue infection.To the best of our knowledge,there have been very few documented cases of Flavivirus causing isolated Bell’s palsy.

PROF.ZHANG ANLI'S EXPERIENCE OF TREATING STUBBORN CASES OF FACIAL PALSY

Based on her own experience of many years＇ clinical practice, Prof. Zhang Anli summarized and created the method in which the shallow insertion at the upper eyelid, acupuncture at the Back-shu points and balanced selection of points together with the modified Setting Mountain on Fire and application of Fire Needle were applied for the treatment of stubborn cases of facial palsy. The therapeutic effect is good.

Bell's palsy at high altitude——an unsuspected finding

Background:Bell's palsy is a common condition seen in clinical practice.The aetiology of this condition is not clearly defined and neuroimaging is essential to exclude intracranial causes of infra-nuclear facial palsy.Case presentation:We report a young soldier,who presented with Bell's palsy and neuroimaging revealed an unsuspected finding of multiple intracranial calcifications.Detailed evaluation revealed the additional diagnosis of vitamin D deficiency and secondary hyperparathyroidism due to lack of sun exposure at high altitude area.Conclusion:The health care practitioners,looking after the soldiers at high altitude areas should be aware of the measures to prevent vitamin D deficiency.Intracranial calcifications are uncommon in hyperparathyroidism and Bell's palsy.

The prevalence of metabolic syndrome in non diabetic patients with a previous history of Bell’s palsy

Objectives: To compare the prevalence and each parameter of metabolic syndrome between non diabetic patients with previous Bell’s palsy and non diabetic healthy subjects. Material and method: A number of 454 Bell’s palsy patients (aged 15 years old and over) were initially recruited as the study group. 874 non diabetic healthy participants of a metabolic syndrome surveillance study were randomized by R program as the control group to make up a 1:3 ratio of case to control. Metabolic syndrome was defined by International Diabetes Foundation criteria. The descriptive statistics analysis, t-test and Chi-Square test were applied for statistical analysis. Results: Seventy two non diabetic, previous Bell’s palsy cases (30 males and 42 females) were eligible as the study group. Their mean age was 51 (39.8 - 63.2) years old. The prevalence of metabolic syndrome in the study and the control groups were 22.2% and 21.8% respectively (p = 0.93). Nevertheless, the prevalence of hypertension was significantly higher in the study group (62.5% vs. 47.7%) (p = 0.04). Conclusions: No difference in the prevalence of metabolic syndrome was found. However, hypertension was significantly prevalent in the study group.

Multifaceted superoxide dismutase 1 expression in amyotrophic lateral sclerosis patients:a rare occurrence?

Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.

Recovery from Bell’s palsy after treatment using uncultured umbilical cord-derived mesenchymal stem cells:A case report

BACKGROUND Bell’s palsy is an idiopathic facial palsy with an unknown cause,and 75%of patients heal spontaneously.However,the other 25%of patients continue experiencing mild or severe disabilities,resulting in a reduced quality of life.Currently,various treatment methods have been developed to treat this disease.However,there is controversy regarding their effectiveness,and new alternative treatments are needed.CASE SUMMARY The patient suffered from left-sided facial paralysis due to Bell’s palsy for 7 years.The patient received an uncultured umbilical cord-derived mesenchymal stem cell transplant eight times for treatment.After follow-up for 32 mo,the paralysis was cured,and there was no recurrence.CONCLUSION Uncultured umbilical cord-derived mesenchymal stem cell transplantation may be a potential treatment for patients with Bell’s palsy who do not spontaneously recover.

Bell’s palsy after inactivated COVID-19 vaccination in a patient with history of recurrent Bell’s palsy: A case report

BACKGROUND With rapid and extensive administration of inactivated coronavirus disease 2019(COVID-19)vaccine to the general population in China,it is crucial for clinicians to recognize neurological complications or other side effects associated with COVID-19 vaccination.CASE SUMMARY Here we report the first case of Bell’s palsy after the first dose of inactivated COVID-19 vaccine in China.The patient was a 36-year-old woman with a past history of Bell’s palsy.Two days after receiving the first dose of the Sinovac Life Sciences inactivated COVID-19 vaccine,the patient developed right-side Bell’s palsy and binoculus keratoconjunctivitis.Prednisone,artificial tears and fluorometholone eye drops were applied.The patient’s symptoms began to improve by day 7 and resolved by day 54.CONCLUSION As mRNA COVID-19 vaccine trials reported cases of Bell’s palsy as adverse events,we should pay attention to the occurrence of Bell’s palsy after inactivated COVID-19 vaccination.A history of Bell’s palsy,rapid increase of immunoglobulin M and immunoglobin G-specific antibodies to severe acute respiratory syndrome coronavirus 2 may be risk factors for Bell‘s palsy after COVID-19 vaccination.

Misdiagnosis of Facial Nerve Palsy: A Case Report of Sporadic Vestibular Schwannomas (Non-NFM2) Causing Facial Nerve Palsy Be Misled by Bell’s Palsy in a Child

We report a case of a rare sporadic Vestibular Schwannoma of a 9-month-old girl who had a right-sided lower motor type facial nerve palsy. The patient was initially diagnosed with Bell’s palsy and received steroid treatment accordingly, two months later the patient’s condition deteriorated, and further evaluation of CT and MRI brain was conducted that showed a mass lesion in the posterior fossa causing compression on the facial nerve. Misdiagnosis of facial nerve paralysis is common among children due to multiple related etiologies and varying rates of incidence in comparison to adults. The authors hope to address this issue in this report. Background: Facial nerve paralysis has been a matter of concern for many researchers to understand its nature, causes and presentation according to different age groups. In adults, Bell’s palsy (BP), the idiopathic form of facial nerve paralysis, is more common compared to children where most cases are due to secondary etiologies. Therefore, pediatricians are in an important position to identify these patients early in order to launch the most effective diagnostic and treatment approaches.

Bell’s Palsy Post COVID-19 Vaccination: A Retrospective Cross-Sectional Study in a Single Tertiary Center

Introduction: Bell’s palsy is an uncommon adverse effect of the COVID-19 vaccine that has been reported in clinical trials. Even though a few studies have linked the vaccination to Bell’s palsy, the actual mechanism is uncertain. Objectives: To describe the demographic data and COVID-19 vaccines-related data with Bell’s palsy in a tertiary centre of Malaysia, Hospital Kuala Lumpur. Methods: A retrospective cross-sectional study was observed among vaccinated recipients who developed Bell’s palsy within 60 days and sought treatment in the Otorhinolaryngology Department Hospital Kuala Lumpur, Malaysia between 1st May 2021 and 30th November 2021. The demographic data, clinical history, and vaccination history were collected from clinical records. The facial paralysis was graded according to the House-Brackmann grading system. Results: A total of 26 patients with a mean age was 38.5 years;higher incidence in younger age, below 60 years old (n = 24), specifically 18 - 30 years old (n = 11). We observed an equal number in relation to gender and onset (after the first or second dose) of facial palsy. Predominantly were Malay (n = 21) and only 6 patients had comorbidities. We found there was no difference in regard to the type of vaccine among Bell’s palsy patients;Pfizer (n = 9), followed by Sinovac (n = 9) and AstraZeneca (n = 8). Conclusion: Bell’s palsy was found to be a possible adverse event of the COVID-19 vaccine. Younger groups were noted as susceptible to this rare adverse effect. However, the benefits of vaccination outweigh the risk of Bell’s palsy, which has a good prognosis. More research with larger samples is needed to determine the true relationship between vaccination and Bell’s palsy.

Electrophsiological study in the prognosis of Bell palsy

AIM:To estimate the prognosis of Bell palsy.METHODS:Blink reflex(BR),electromyography(EMG),motor latency(ML )and amplitude(AMP )of facial nerve were performed in 42p atients with Bell’ s pal-sy.The patients were followed about half a year.RESULTS:(1)When 1of the 3R waves related with the ill side existed or appeared in 3weeks after onset,97%patients could reco ver completely.The recovery time wa s related to the time of the occurrence of R wave.(2)When 1of the 3R waves appeared in the 4th week,60%patients could recover complete-ly.When none of the 3waves appeared a fter the 4th week,100%patients could not recover completely.EMG sh owed spontaneous activities in 3of the 6patients in the 4th week.(3)Motor latency and amplitude of facia l nerve were examined when the illness stopped developing.All patients had normal latencies.5patients’ amplitudes reduced more than 90%.3o f the5patients did not appear the related R waves after the 4th week.CONCLUSION:BR might provide the early sign of good prognosis of Bell’ s palsy.BR together with EMG and ML an d AMP of facial nerve might provide the later sign of poor p rognosis.