Efficacy of Thiamine in Patients With Clinically Suspected Dry Beriberi: An Open Labeled Hospital Bases Study in Bangladesh
Phase: NA
Conditions: Dry Beriberi
Sponsor: Chittagong Medical College

 

Efficacy of Thiamine in Patients with Clinically Suspected Dry 
Beriberi: An open labeled Hospital 
Based Study 
 
Principal investigator: 
 
Dr. Nayema Masrura 
MD (Neurology), 3rd part student, 
Department of Neurology, 
Chittagong Medical College Hospital. 
 
 
Guide: 
Dr. Md. Hassanuzzaman 
FCPS (MEDICINE), MD (NEUROLOGY) 
Associate Professor and Head, 
Department of Neurology, 
Chittagong Medical College Hospital. 
 
 
Co-Guide: 
Dr. Mahbubul Alam Khandakar 
FCPS (MEDICINE), MD (NEUROLOGY) 
Assistant Professor, 
Department of Neurology, 
Chittagong Medical College Hospital  
 
 

The Chairman, 
Ethical review Committee, 
Chittagong Medical College, 
Chittagong. 
 
Subject: Submission of thesis protocol 
 
Sir, 
 
With due respect this is for your kind information that I am a MD (Neurology) 3rd Part 
student and bound to perform a research work in the respective discipline during my 
course tenure. Before commencement of a research work however it is mandatory to 
make it ethically approved, henceforth, I would like to submit my thesis proposal seeking 
ethical permission. To be more, the title of proposed thesis is “Efficacy of Thiamine in 
Patients with Clinically Suspected Dry Beriberi: An open labeled Hospital Based 
Study” for ethical approval. 
 
I, therefore, pray and hope that you would be kind enough to approve the above to begin 
my thesis work and oblige thereby. 
 
Faithfully yours 
 
Dr. Nayema Masrura 
Student of MD (Neurology) 3rd part 
Chittagong Medical College 
Chittagong. 
 
 
 
 

APPLICATION FOR ETHICAL REVIEW OF THESIS PROPOSAL 
[Application is to be submitted with the thesis proposal and protocol] 
 
Name of the students: Dr. Nayema Masrura 
Subject: Neurology  
Roll No. Not applicable  
Course: MD  
Session: 2006-07 
Category: Government 
 
Title: “Efficacy of Thiamine in Patients with Clinically Suspected Dry Beriberi: An 
open labeled Hospital Based Study” 
Supervisor/ Guide: 
 
Dr. Md. Hassanuzzaman 
Associate Professor & Head , 
Department of Neurology, 
Chittagong Medical College and Hospital 
 
Co-guide: 
 
Dr. Mahbubul Alam Khandakar 
Assistant Professor, 
Department of Neurology, 
Chittagong Medical College and Hospital 
______________________________________________________ 
□ 3 hard copies of the thesis proposal and protocol 
□ 1 CD of the thesis proposal and protocol 
Submission Date: ____________________ 
Signature of the Student: ______________________________________ 
For Official Use 
Serial No: _________________Received on: __________________ Reviewed 
on:___________ 
Comment:_____________________________________________________________ 
 
Member-Secretary ERB                                               Chairperson ERB 

CMC Ethical Review Committee 
Chittagong Medical College 
Chittagong 4203, Bangladesh 
Tel: 619400 Fax: 630180 Email: cmc@fnfbd.net 
(Application for Ethical Clearance for Studies for Post Graduate Thesis proposal) 
1. Name of the applicant: Dr. Nayema Masrura 
2. Course: MD (Neurology) 
3. Category: Government 
4. Title of the study: “Efficacy of Thiamine in Patients with Clinically Suspected Dry 
Beriberi: An open labeled Hospital Based Study” 
5. Type of the study: A Quasi experimental study. 
6. Duration: Twelve (12) months 
7. Any collaboration: This study will be conducted in neurology department in 
collaboration with department of Internal medicine, Chittagong medical College 
Hospital. 
8. Conflict of interest disclaiming: Not applicable 
9. Supervisor:                                                                   
 
                                                                                  Dr. Md. Hassanuzzaman 
                                                                                  Professor & Head 
                                                                                  Department of Neurology, 
                                                                                  Chittagong Medical College Hospital. 
Co-guide:                                                                
 
                                                                             Dr. Mahbubur Alam Khandakar 
                                                                             Assistant Professor 
                                                                             Department of Neurology, 
                                                                             Chittagong Medical College Hospital10. 
10. Abstract of study: Attached here with. 

Put ✔ mark the appropriate answer to each of the following (If not Applicable write NA) 
 
1. Source 
Population: 
 
 
4. Are subjects clearly 
informed about: 
 
 
(a) Ill Subjects  
✔Yes  
No  
(a) Nature and purpose of 
the study 
✔Yes  No 
(b) Non ill subjects  
Yes  
✔No  
(b) Procedures to be 
followed including 
alternatives used 
✔Yes  No 
(c) Minors or persons 
under guardianship 
Yes  
✔No  
(c) Physical risks  
✔Yes  No 
2. Does the study 
involve:  
Yes  
No 
(d) Private questions? 
✔Yes  No 
(a) Physical risks to 
subjects 
Yes 
✔No 
(e) Invasion of the Body 
✔Yes  No 
(b) Social risks 
Yes  
✔No  
(f) Benefits to be derived  
✔Yes  No 
(c) Psychological 
risks to subjects 
Yes  
✔No  
(g) Right to refuse to 
participate or withdraw 
from the study 
✔Yes  No 
(d) Discomfort to 
subjects 
Yes  
✔No  
(h) Confidential 
handling of data  
✔Yes  No 
(e) Invasion of the 
body 
✔Yes  
No  
(i) Compensation where 
there are risks or loss of 
working time or privacy is 
involved in any particular 
procedure 
✔Yes  No 
(f) Invasion of 
privacy 
Yes  
✔No 
5. Will signed 
consent/verbal consent be 
required 
 
 
(g) Disclosure of 
information 
damaging to subject 
or others  
Yes  
✔No 
(a) From Subject 
✔Yes  No 
3. Does study 
involve: 
 
 
(b) From parents or 
Guardians 
✔Yes  No 
a) use of records 
(hospital, medical, 
death,birth or other) 
Yes  
✔No 
6. Will precautions be 
taken to protect 
anonymity of subjects 
 
✔Yes  No 
b) use of fetal tissue 
or abortus 
Yes  
✔No 
 
 
 
c) use of organs or 
body fluid 
Yes  
✔No 
 
 
 

 
Check documents being submitted herewith to committee 
# Abstract: 
# Umbrella proposal initially: 
# Protocol and CRF: 
# Informed consent form for subjects: 
# Informed consent form for parents: 
# Verbal consent form for subjects: 
# Procedure for maintaining confidentiality: 
# Schedule of the study 
 
 
 

Declaration 
 
I agree to obtain approval of the Ethical Review Committee for any changes 
involving the rights and welfare of subjects or any changes of the 
methodology before making any such changes. 
 
 
 
 
 
 
 
Dr. Nayema Masura 
MD ( Neurology) 3rd Part 
Department of neurology, 
Chittagong Medical College. 
 
 

 
Forwarding of the Guide/Supervisor 
 
This is to certify that Dr. Nayema Masrura, is proposed to carry out research 
work titled “Efficacy of Thiamine in Patients with Clinically Suspected 
Dry Beriberi: An open labeled Hospital Based Study” and prepared this 
research proposal under my direct supervision. 
 
 
 
 
 
 
 
 
 
 
Dr. Md. Hassanuzzaman 
FCPS (MEDICINE), MD  (NEUROLOGY 
Associate Professor & Head 
Department of Neurology, 
Chittagong Medical College and Hospital 
 
 
 
 

Chittagong Medical College 
Research cell 
Chittagong- 4000, Bangladesh 
Tel-619400, fax-630180, E-mail: cmc@fnfbd.net 
Research Proposal 
For postgraduate Thesis/Dissertation 
 
Part—A 
1. Thesis title : “Efficacy of Thiamine in Patients with Clinically Suspected Dry 
Beriberi: An open labeled Hospital Based Study” 
2. Student's name : Dr. Nayema Masrura 
3. Course : MD (Neurology) 
4. Place of study : Chittagong 
5. Duration : 12 Month 
6. Date of commencement: July 2018 
7. Date of completion: June 2019 
8. Sponsoring agencies: not applicable 
9. Total cost : Tk. 250,000/ (Two hundred and fifty thousand only) 
10. Other support for proposed research: 
(i) Is this research being supported by any other source?-NO 
(ii) Has an application for funding of this project been submitted to any other 
organization?-NO 
11. Date of submission: 02/05/2018 
12. Signature of the student: 
 
13. Signature of the Guide: 
 
14. Signature of Course Co-ordinator: 
 

PART-B 
 
STUDENT'S INFORMATION SHEET 
 
1. (i) Name: Dr. Nayema Masrura 
(ii) Designation: MD Neurology Student 
(iii) Official Address with telephone: 
Ward: 18, Neurology Department, 
Chittagong Medical College, Chittagong, 
(iv) Present Residential Address with telephone: 
94/A, Santibug R/A, Chotopole,North Agrabad, Ctg 
Mobile No- 01817743838 
2 .Academic Background: 
 
 
 
3. Field of Specialty: Neurology 
4. (a) Research Experience: N/A 
(b) Other Experience: Nil 
5. Percentage of time to be devoted to this project: Full time 
6. Number of Scientific Publications: Nil  
Degree  
Institute  
Board/University  
Result  
year 
MBBS  
Chittagong 
Medical College 
Chittagong university  
Pass  
2004 
HSC  
Chittagong 
College 
Chittagong board  
1st division  
1997 
SSC  
Chittgong Port Authority 
Girls'High School 
Comilla board  
1st division  
1995 

Part-C 
Abstract: 
In our day to day clinical practice we have encountered many of them with neurological 
complaints mimicking thiamine deficiency (TD). Investigations to confirm this condition 
are not available in our setting. So, the diagnosis of TD in such contexts is a real 
challenge and a high level of clinical suspicion should be demonstrated in such situations. 
Early treatment with thiamine has the potential to rapidly reverse clinical signs and 
minimize sequelae, before the onset of fixed lesions. The lack of diagnostic capacity in 
our settings justifies the use of a therapeutic thiamine challenge in cases with high 
clinical suspicion. However, there is paucity of study about the clinical spectrum and 
therapeutic response of such patients in Bangladesh. The aim of this prospective hospital 
based quasi-experimental study will be to determine the clinical pattern of patients with 
suspected dry beriberi and their outcome to thiamine therapeutic challenge in our setting. 
Fifty-five patients of clinically suspected dry beriberi will be enrolled as per inclusion 
and exclusion criteria. Then therapeutic trial of Inj. Thiamine will be given IV for 1st 
week (200mg IV daily for peripheral neuropathy and then orally (tab. Thiamin 100mg 
bd) for 11 weeks. Patients will be followed up after 1, 6 and 12 week to see the response. 
Pre and post treatment data will be recorded in pre designed case record form. To 
determine whether any of the difference between pretreatment and post treatment values 
were statistically significant or not, either Friedman’s test or Cochran’s Q test were used. 
Former test compares the quantitative variables and non-dichotomous qualititative 
variables and the later test compares the dichotomous qualitative/categorical variables. 
Statistical significance were defined as P < 0.05 and confidence interval was set at 95% 
level. Analysis will be performed with SPSS version 23. Our study result is likely to 
sensitize the health professionals of this region about this neglected health issue by 
increasing awareness of the clinical spectrum of Thiamine Deficiency related Peripheral 
Neuropathy. Moreover, study may provide the impetus for fashioning national policies on 
the diagnosis, treatment and prevention of thiamine deﬁciency disorders in our country.  

Part-D 
1. Introduction: 
According to World Health Organization (WHO) International Nomenclature of 
Diseases, Thiamine deficiency (TD) syndrome is a clinical syndrome that arises 
insidiously as a result of a severe, prolonged deficiency of thiamine in the diet, 
manifested in the initial stages by anorexia, malaise, and weakness of the legs, frequently 
with paraesthesia; there may be slight oedema and palpitations.  The disorder may persist 
in this chronic state or may at any time progress to an acute condition characterized either 
by cardiac involvement with oedema or by peripheral neuropathy; forms intermediate 
between these two extremes may also occur.  It is thought that the basic cause is the 
inhibition of a series of enzyme-catalysed cleavages of carbon-carbon bonds in which 
thiamine diphosphate is a coenzyme. Commonly used synonyms are beriberi; Ceylon 
sickness; occidental beriberi (in part); oriental beriberi (in part); rice disease etc. The 
disorder (or spectrum of disorders) is classically associated with a diet consisting largely 
of  polished rice (oriental beriberi), but may also arise if highly refined wheat flour forms 
a major part of the diet, in alcholics, and in food faddists (occidental beriberi).1  
Thiamin (vitamin B1) is widely distributed in foods of both vegetable and animal origin. 
It is an essential micronutrient with dual coenzymatic and non-coenzymatic functions. It 
is involved in carbohydrate and branched-chain amino acid metabolism, as well as in the 
production of neurotransmitters, myelin, and nucleic acids. There is also evidence that 
thiamine plays a role in immune and anti-inflammatory processes and gene regulation.2-5 
The human body requirement for thiamine is exclusively dependent on regular dietary 
intake, as there is no signiﬁcant mechanism for endogenous production of thiamine or for 
prolonged storage of thiamine in the human body. It is estimated that the body can store 
thiamine for 2–3 weeks. Staple diets that are deﬁcient in thiamine would result in low 
body thiamine levels, which may be subclinical or may manifest as a thiamine-deﬁciency 
syndrome. Thiamine deﬁciency is classically associated with diets consisting mainly of 

milled white cereals, particularly polished rice and highly reﬁned wheat ﬂour. Milling 
signiﬁcantly reduces the thiamine content of cereals: the thiamine content of highly 
milled white rice is 0.08 mg/100 g compared with 0.33 mg in unmilled brown rice. Rice 
washing and cooking methods may result in additional losses of up to 45–60% of 
thiamine. Rice is the most important food source in our country. The combination of 
limited body storage and a high turnover rate (half-life <10 days) results in potential 
depletion of thiamine stores within 2 weeks if it is not continuously replaced. In addition, 
thiamine’s hydrosolubility, coupled with its renal clearance profile, contributes to a 
propensity to thiamine deficiency (TD) throughout life.1,6 
It principally affects precarious communities where children and adults are most 
vulnerable and where dietary habits rely on refined processed cereals or tubers (e.g., rice, 
wheat, cassava), notably in Southeast Asia and Africa. TD can result from various 
mechanisms that are not mutually exclusive. The most frequent mechanisms are 
insufficiency of dietary thiamine (enteral–parenteral supply) and poor intestinal 
absorptive capacity during malnutrition, tropical enteropathy, or secondary to surgical 
resection of large portions of the gastrointestinal tract. A relative inadequacy of thiamine 
content to caloric ratio (high carbohydrate diets) is also common. It is this thiamine–
calorie imbalance that is responsible for TD in heavy drinkers of sweet drinks and 
contributes to the onset of TD when dextrose-based fluids are administered without 
thiamine supplementation in critically ill patients. Poor thiamine intake may be due to 
losses from food secondary to pre-cooking and food processing (e.g., repetitive rice 
washing), a restrictive diet due to cultural habits and ingestion of antithiamine factors (tea 
leaves, betel nuts, and coffee) or thiaminases (e.g., fermented raw fish, mycotoxins, 
stored food, and larvae) that break down and, thus, inactivate thiamine. Excessive loss of 
thiamine from the body, such as renal (loop diuretics, osmotic diabetic diuresis) or 
digestive losses (chronic diarrhea, hyperemesis), can also precipitate TD. At cellular 
level, two main mechanisms contribute to TD – impaired uptake or increased demand. 
Impaired cellular uptake of thiamine can be due to defects in thiamine transporters or 
specific enzymes (mutation, hypomagnesemia, drug-induced interaction), or reduced 

levels of ThDP. Increased cellular demand of thiamine occurs in hypermetabolic states 
during critical illness, e.g., severe infections, shock, burns, fever, hyperthyroidism. 
Exposure to toxic substances, such as alcohol can also affect thiamine metabolism. When 
this occurs during pregnancy, the fetus may be indirectly affected, as observed in fetal 
alcohol syndrome. Maternal TD associated with excessive alcohol consumption is usually 
secondary to inadequate thiamine intake or decreased intestinal absorption due to reduced 
expression of ThTr-1. In addition, impaired intracellular thiamine utilization affecting the 
TPK activity results in a low bioavailability of the active cellular ThDP due to ethanol 
and acetaldehyde exposure. In humanitarian fields, TD occurring in epidemic proportions 
has been described following abrupt food shortage caused by disasters, famines, conflicts, 
or large population displacement.7   
 
TD in adult may be be manifestated in three forms: TD with peripheral neuropathy, TD 
with cardiomyopathy and TD with lactic acidosis.  TD with peripheral neuropathy is an 
acute form of thiamine deficiency characterized by polyneuropathy with paraesthesia of 
the extremities (especially the legs), reduced knee jerk and other tendon reflexes, and 
progressive severe weakness and wasting of  muscles; the susceptibility to infections is 
greatly increased. Synonyms are  atrophic beriberi; dietetic neuritis (in part); dry beriberi; 
endemic polyneuritis; panneuritis endemica; paralytic beriberi; polyneuritis endemica. 
The neurological signs constitute dry beriberi are evident even in the early stages. 
Polyneuritis and paralysis of the periphgeral nerve predominate; the central nervous 
system is scarcely involved. Manifestations are seen in the autonomic, sensory and motor 
systems. The autonomic nervous system is functionally altered in the early course of 
disease, as the clinical and pharmacological findings in beriberi patients suggest. In the 
sensory system, tactile sensation is the first affected, then there is pain, and finally 
temperature sensitivity altered. The sensory disturbances are usually not so marked as to 
be termed ‘anesthesia’, but superficial hyperesthesia is more or less characteristically 
distributed, beginning in the lower extremities, finger tips, lower abdomen and perioral 

areas and gradually expanding. The sensory effects are usually symmetrical although the 
side that is greater use tends to be affected first. Paraesthesia is often the earliest sign of 
diminished sensitibility and the patients complains of burning sensation in the legs and 
toes. Although rare, sensory disturbances of the oral cavity are encountered in a few 
cases. Paralysis of the motor nerves occurs after the sensory disturbances.  This also 
begins in the tips of the lower extremities, then in the fingers, and ascends progressively.  
There is increasing muscular weakness which is readily demonstrated by the inability of 
the individual to rise from a squatting position without assistance and, as the disease 
progresses, there is atrophy of the leg muscles.  The tendon reflexes are also affected 
especially with loss of ankle and knee jerks. Painful calf muscles and, eventually, foot 
drop and, later, wrist drop may also develop. Advanced neurological changes may result 
in great difficulty in walking and may even lead to complete paralysis. Frequently, 
vertigo and instability of the body during walking are noted in beriberi patients. The 
shaky gait is equivalent to positive Romberg’s sign and mostly caused by impaired 
vestibular function in advanced cases although it is partially due to decrease deep 
sensations. Nystagmus, as a sign of manifestation of vestibular malfunction, has been 
reported to occur particularly in alcoholics who developed Wernick’s encephalopathy. 1,6 
Epidemics of beriberi manifesting with sensory neuropathy and gait ataxia have been 
described in children and adults within segments of the African population subsisting on 
diets that provide marginal or submarginal intakes of thiamine8 in prison populations9,10 
and in garrisoned troops.11 Seasonal ataxic syndrome is an acute thiamine deﬁciency state 
that has occurred in epidemics in parts of Western Nigeria during the rainy season and 
manifested with clinical features of Wernicke’s encephalopathy. Studies have conﬁrmed 
that seasonal ataxic syndrome is a thiamine-deﬁciency disorder that occurs in low-income 
individuals with marginal thiamine deﬁciency. Tropical ataxic neuropathy (TAN) is a 
syndrome of sensory polyneuropathy, sensory ataxia, bilateral optic atrophy, and bilateral 
sensorineural deafness described in several African countries. The cardinal 
clinicalfeatures of TAN are similar to those of thiamine deﬁciency.12 A therapeutic trial 
of thiamine in these patients has indicated that it is a thiamine deﬁciency state.13 

Besides there are some clinical conditions which may probably be results from TD. There 
are some neurologic syndromes of undetermined etiology occurring in parts of Africa that 
are probable thiamine-deﬁciency syndromes but have not been conclusively investigated 
and conﬁrmed to be due to thiamine deﬁciency. One of these is epidemic spastic 
paraparesis (konzo), a severely debilitating disorder characterized by abrupt onset of 
paraplegia occurring in patients subsisting almost exclusively on a diet of improperly 
processed cassava roots.14 Epidemics have been reported from several countries in 
Central and East Africa affecting hundreds of thousands of people, predominantly 
children and young women. The etiology remains unknown, but several aspects of the 
clinical presentation are suggestive of a thiamine-deﬁciency disorder.12 Thiamine levels 
have never been tested in these patients, and at herapeutic trial of thiamine has never been 
performed. Another probable thiamine-deﬁciency disorder is the epidemic optic 
neuropathy associated with peripheral neuropathy, which has been reported in Tanzania 
and Somalia.15,16 The clinical description of the syndrome is quite similar to the epidemic 
of optic and peripheral neuropathy described in Cuba, where patients were found to be 
thiamine deﬁcient and responded to vitamin B supplementation.17  The epidemic optic 
neuropathy syndrome may well be a forme fruste of TAN, which also presents with optic 
neuropathy and peripheral neuropathy. Although acute cases of epidemic optic 
neuropathy have been successfully treated with vitamin B supplementation in Tanzania,16 
thiamine levels have never been tested in these patients, and a therapeutic trial of 
thiamine has never been conducted. 
 
Thiamine deficiency can be investigated using plasma, erythrocytes, whole blood ThPP 
levels and urinary excretion of thiamine before and after exogenous thiamine 
administration.18 However, serum or whole blood thiamine has poor sensitivity and 
specificity in severe acute conditions as it decreases during systemic inflammation, and 
represents only a small part of the whole body thiamine pool. Erythrocyte transketolase 
activity more accurately evaluates the thiamine status of the body and is, therefore, used 

as standard.19 MR imaging showing specific lesions can also be very helpful in early 
detection of neurologic features of TD in children. However, none of these investigations 
allow immediate diagnosis of TD in life-threatening conditions and they are rarely 
available in resource-limited settings. Consequently, the diagnosis of TD in such contexts 
is a real challenge, especially considering its wide and non-specific clinical spectrum and 
potentially fatal prognosis. A high level of clinical suspicion should be demonstrated in 
the following situations: suspicion of infantile beriberi; unexplained neurological signs, 
encephalitis, and cardiac failure; early clinical deterioration after initiation of feeds in 
malnutrition; sepsis (including in SAM); severe burns; major trauma; hypoxia; and 
unresponsive lactic acidosis. However, in the absence of specific diagnostic tests, the 
only way to diagnose TD is to carry out a therapeutic thiamine challenge. Considering its 
safety profile and wide dosage range, in such cases, thiamine can be administered by 
slow intravenous injection over 30 min. In severe acute conditions caused by TD, rapid 
clinical improvement will be seen (within hours or days) following thiamine 
administration.7  
Thiamine deficiency global prevalence is poorly documented. Despite being easily 
treatable, TD continues to be seen in all age groups in both high and low resource 
countries with potentially severe and life-threatening consequences.7 Chittagong Medical 
College Hospital is the second largest tertiary level hospital in Bangladesh. It provides 
different specialist service mostly to the patients of south-eastern part of Bangladesh. It 
has a rich Neurology department. In our clinical practice we have encountered patients 
especially from Satkania, Bashkhali, Cox’sbazar, Teknaf, Saintmartin, Mosheskhali 
upazillas of Chittagong Division with neurological features mimicking TD. Most of them 
are from low socio-economic strata. They are at risk of developing TD syndrome for their 
dietary habit. In our experience most of them show positive response to therapeutic trial 
of thiamine.  However, there is paucity of any survey or systemic study in this issue.  
This situation has stimulated us to design this study to evaluate the clinico-
epidemiological features of these patients and to assess their response to thiamine trial in 
a systematic way. 

2.Research questions: 
 What is the clinic-epidemiological profile of adult patients with suspected dry 
beriberi ? 
 How do they response to therapeutic thiamine challenge?  
 
3. Objectives:  
3.1 General objective: 
 To evaluate the efficacy of Thiamine in patients with suspected / possible dry 
beriberi 
3.2 Specific objectives: 
1. To describe the socio-demographic profile of  patients 
2. To categorize the patients according to their presenting symptoms and signs. 
3. To assess and compare pre and post treatment neurological features 
 
 
 

4. Rationale: 
A vast population of southern area of Chittagong division of Bangladesh (Satkania, 
Bashkhaki, Cox’sbazar, Teknaf, Moheshkhali, Saint martin) are at risk of developing 
thiamine deficiency syndrome due to their dietary habit and low socio-economic 
condition. In our day to day clinical practice we have encountered many of them with 
neurological complaints mimicking thiamine deficiency (TD). However, TD has a large 
clinical spectrum, and as such it is frequently misdiagnosed, sometimes with fatal 
consequences or permanent neurological sequelae. TD can be investigated using plasma, 
erythrocytes, whole blood ThPP levels, and urinary excretion of thiamine before and after 
exogenous thiamine administration. But none of these investigations allow immediate 
diagnosis of TD in life-threatening conditions and they are rarely available in resource-
limited settings. So, the diagnosis of TD in such contexts is a real challenge and a high 
level of clinical suspicion should be demonstrated in such situations. Early treatment with 
thiamine has the potential to rapidly reverse clinical signs and minimize sequelae, before 
the onset of fixed lesions. The lack of diagnostic capacity in our settings justifies the use 
of a therapeutic thiamine challenge in cases with high clinical suspicion. It is an effective, 
inexpensive, and easy to administer medication.  
This issue of dry beriberi has got less attention and in our extensive literature search we 
have failed to identify any document related to dry beriberi in this part of Bangladesh. So, 
it is rational to design a prospective study to determine the clinical pattern of patients 
with suspected dry beriberi and their outcome to thiamine therapeutic challenge in our 
setting. Our study result is likely to sensitize the health professionals of this region about 
this neglected health issue by increasing awareness of the clinical spectrum of TD. 
Moreover, study may provide the impetus for fashioning national policies on the 
diagnosis, treatment and prevention of thiamine deﬁciency disorders in our country.  
 
 

5. Metarials and methods: 
5.1 Type of study: Quasi-experimental study, self –controlled clinical trial (pretest –
posttest design) 
5.2. Period of study: One year. 
5.3. Place of study: Department of Neurology, Department of Medicine of 
Chittagong Medical College Hospital. 
 5.4. Study population: All the patients admitted in the above mentioned ward 
of CMCH with clinical diagnosis of suspected dry beriberi. 
5.5. Sampling technique: Required number of patients will be selected purposively as 
per set criteria 
5.6. Eligibility criteria:  
Inclusion criteria: 
1. Any person admitted to CMCH as a Suspected/Possible dry-beriberi. 
Risk factors + at least 2 of the following signs: 
Risk factors include Imbalanced diet (diet poor in thiamine/rich in carbohydrate or anti-
thiamine factors), malnutrition, alcoholism, GIT surgery, chronic diarrhoea, chronic 
vomiting, pregnancy or history of recent delivery, chronic. diuretics use, renal dialysis, 
total parenteral nutrition. 
 
a) Muscle weakness of upper and or lower limb (less than grade 5 power in MRC 
scale) 
b) Positive sensory symptoms (burning, tingling or pain) 
c) Objective sensory deficit (pain, touch, position, vibration sense ) 
d) Absent or reduced deep tendon reflexes 
e) Positive squat test (unable to rise after squatting without help) 
f) Leg swelling 
 
2. Age 18 years and above 

Exclusion criteria:  
1. Patients with isolated cardiac/wet beriberi 
2. Patient with known causes of peripheral neuropathy such as Diabetic, 
hereditary, 
Demyelinating 
(GBS, 
CIDP), 
metabolic 
(hepatic/renal 
impairment), drugs (e.g. INH, Ethambutol, Phenytoin, Metronidazole, 
Dapsone etc.) Toxin (As ,OPC, Pb ,Hg except alcohol) etc. 
3. Patients refuse to participate 
 
 
5.7. Sample size: 
To estimate the prevalence following formula will be used to determine the sample size 
by doing finite population correction: 
𝑛=
𝑧2𝑝𝑞𝑁
𝑑2 × (𝑁−1) + 𝑧2𝑝𝑞 
Where,  
n= required sample size, 
z= z-value of standard normal distribution at a given level of significance 
p=prevalence of the event (Prevalence of clinically suspected dry beriberi patients 
show positive response to thiamine trial, usually from previous study) 
q=100-p 
d= allowable error/precision in the estimate of ‘p’= usually 10% of p 
N= Expected number of suspected dry-beriberi patients admitted in Neurology 
and Medicine department of CMCH during data collection period. 
Here,  

z= 1.96 at 95% confidence level 
p=80%=0.8[Prevalence of clinically suspected dry beriberi patients show positive 
response to thiamine trial is not available from extensive literature search. 
However, from our experience, 80% of these patients show positive response]. 
q= (100-80) %=20%=0.2 
d=10% of p= .1×.7=.08 
N= 75 
So, 𝑛=
1.962×0.8×0.2×75
(.08)2×(75−1)+1.962×0.8×0.2 = 41.6 ≈42 
However, final sample size will be increased to 55 assuming 30% drop out. 
5.8. Data collection tool:  
 A predesigned Case Record Form.  
5.9. Procedure of collecting data:  
All patients attending the above mentioned ward with a diagnosis of suspected dry 
beriberi will be assessed for eligibility. Informed written consent will be obtained from 
the patients or attendants after full explanation of the ultimate outcome, complications 
and purpose of the study. They will be informed of their right to withdraw from the study 
at any stage. After consenting, the details of the patient’s history including demographic 
information, food habit, clinical findings at presentation, results of laboratory, and 
neuroimaging testing will be recorded in case record form.  A general physical 
examination (e.g. pulse, blood pressure, respiratory rate), neurological examination 
(higher mental function, cranial nerves, Motor, sensory, cerebellar function), results of 
laboratory and electro-diagnostic testing (if necessary) were recorded in case record form. 
Then therapeutic trial of Inj. Thiamine is given IV for 1st week (200mg IV daily) then 
orally (tab. Thiamin 100mg bd) for 12 weeks. Patients will be followed up after 1, 6 and 
12 week to see the response. 

5.10. Data analysis: 
All the data will be checked and edited after collection. Continuous data will be reported 
as the means ± SD or median and itraquartile range. Qualitative or categorical data will 
be described as frequencies and proportions. Proportions will be compared using chi-
square or Fisher’s exact test whichever will be applicable. To determine whether any of 
the difference between pretreatment and post treatment values were statistically 
significant or not, either Friedman’s test or Cochran’s Q test were used. Former test 
compares the quantitative variables and non-dichotomous qualititative variables and the 
later test compares the dichotomous qualitative/categorical variables. Statistical 
significance will be defined as P < 0.05 and confidence interval will be set at 95% level. 
SPSS (Statistical Package for Social Science) for Windows version 23 software will be 
used for the analyses. 
5.11. Variables under study: 
Primary Outcome Variable: 
      1. Treatment response measured by Overall Neuropathy Limitation Scale (ONLS) 
score before and after treatment. 
Secondary Outcome Variables: 
1. Comparison and Assessment of clinical features at presentation and after 
treatment: leg swelling, muscle cramp, muscle power (MRC grading), deep tendon 
reflexes, sensory impairments (tingling /burning /pain/ touch/ position /vibration), 
squat test. 
 
5.12 Operational definition: 
Risk factors: Imbalanced diet (diet poor in thiamine/rich in anti-thiamine factors), 
malnutrition, alcoholism, GIT surgery, chronic diarrhora, chronic vomiting ,pregnancy, 
diuretics, renal dialysis, total parenteral nutrition. 
Anti-Thiamine factors: Raw or fermented fish,shell fish,ferns, Tea, coffee, betel nuts 

Possible/suspected dry beriberi: Risk factors + at least 2 of the following signs: 
a) Muscle weakness of upper and or lower limb (less than grade 5 power in MRC 
scale) 
b) Positive sensory symptoms (burning, tingling or pain) 
c) Objective sensory deficit (pain, touch, position, vibration sense ) 
d) Absent or reduced deep tendon reflexes 
e) Positive squat test (unable to rise after squatting without help) 
f) Leg swelling 
 
Probable dry beriberi: Above symptoms recovered after thiamine treatment. 
Socio-economic status: It will be measured as per Modified Kuppuswamy Socio-
economic scale (Appendix-A) and grouped into five categories :Upper class, Upper 
middle class, Lower middle class, Upper  lower class and Lower class. 
5.14. Utilization of results:  
This study result will be helpful to formulate a guideline for the management of 
suspected case of dry beriberi in our setting and improve the outcome of beriberi by 
reducing over or under treatment. Further research on such procedure can be designed by 
utilizing the results of this study. 
 
6. Facilities: 
Administrative setup and resource persons are available in the study site. 
7. Approval of the head of the research cell and ERC:  
Under consideration. 
 
 

8.    Clarification of the ethical issue: 
1. Voluntary consent will be taken from each patient to be enrolled for the forthcoming 
study. patient’s legal guardian  will be approached where required.   
2. All measures will be taken to preserve patients’ anonymity and privacy. To do such, 
a separate case record form (CRF) will be utilized for every patient issuing a different 
identity code and only principal investigator will have access to patients’ data. To be 
more, personal information of any of them will not be handed over any third party 
without their consent.  
3. Evaluation of each research participant will be done thoroughly. Required 
investigations including radio-imaging and biochemical tests will be done in the 
CMCH if facilities available. 
4.They will be treated as per treatment guideline for the disease of research interest. 
Importantly, no financial support will be provided to any research participant for being 
a subject in the research work.  
5. All patients’ will be informed about the nature and purpose of the study. They will 
get informed that their participation in the coming study research will not only benefit 
them but also the whole community as well.  
 
 
 
 

5.13. Flow Chart of Study Design: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient with suspected dry beriberi admitted in 
neurology & medicine ward of CMCH 
History, clinical examination & baseline investigations  
(Including CSF examination, NCS, OGT Test, etc.) 
By inclusion and exclusion criteria, patients of suspected dry beriberi will 
be selected for the study  
Collection of the test results and completion of the CRF 
Sample population will be given Therapeutic 
trial of Thiamine 
Therapeutic response will be assessed on 1st, 
6th and 12th week after treatment and will be 
compared with baseline values.  

5.15 Time schedule: 
 
 
 
 
item 
July  to 
August 
2018 
September 
to October 
2018 
November 2018 
to April 2019 
May 
2018 
June 
2019 
1 
Literature 
search & 
protocol 
writing 
 
 
 
 
 
2 
Piloting & 
CRF(Case 
record form) 
Finalization  
 
 
 
 
 
 
3 
Data 
collection  
 
 
 
 
 
 
4 
Data entry  
 
 
 
 
 
 
5 
Data analysis  
 
 
 
 
 
 
6 
Report 
writing  
 
 
 
 
 
 
7 
submission 
 
 
 
 
 

References:  
1. WHO & UNHCR. 1999. Thiamine deﬁciency and its prevention and control in 
major emergencies. WHO/NHD/99. 13. 
2. Manzetti S, Zhang J, van der Spoel D. Thiamine function, metabolism, uptake, 
and transport. Biochemistry 2014;53(5):821–35. doi:10.1021/ bi401618y  
3.  Singleton CK, Martin PR. Molecular mechanisms of thiamine utilization. Curr 
Mol Med (2001) 1(2):197–207. doi:10.2174/1566524013363870  
4. Bettendorff L. Thiamine in excitable tissues: reflections on a non-cofactor role. 
Metab Brain Dis 1994;9(3):183–209. doi:10.1007/BF01991194  
5. Bettendorff L, Wins P. Biological functions of thiamine derivatives: focus on 
non-coenzyme roles. OA Biochem (2013) 1(1):10. doi:10.13172/2052-9651 5. 
6. Katsura, 
E, 
Oiso 
T. 
Beaton, 
GH, 
Bengoa, 
JM. 
eds. "Chapter 
9. 
Beriberi" (PDF). World Health Organization Monograph Series No. 62: Nutrition 
in Preventive Medicine. Geneva: World Health Organization.1976. 
7. Laurent H, Benjamin R, Nadia L, Daniel M. Thiamine Deficiency in Tropical 
Pediatrics: New insights into a Neglected but vital Metabolic Challenge. Frontiers 
in Nutrition 2016;3(16). doi: 10.3389/fnut.2016.00016. 
8. Tang, C.M., J.C. Wells, M. Rolfe, et al. 1989. Outbreak of beriberi in the Gambia. 
Lancet 2: 206–207.  
9. Ahoua, L., W. Etienne, F. Fermon, et al. 2007. Outbreak of beriberi in a prison in 
Cote-d’Ivoire. Food Nutr. Bull. 28: 283–290.  
10. deMontmollin, D., J. Macphail, J. McMahon, et al. 2002. Outbreak of beriberi in a 
prison in West Africa. Trop. Doct. 32: 234–236. 
11. Watson,J.T.,H.ElBushra,E.J.Lebo,etal.2011.Outbreakof beriberi among African 
union troops in Mogadishu, Somalia. PLoS One. 6: e28345.  
12. Adamolekun, B. 2011. Neurological disorders associated with cassava diet: a 
review of putative etiological mechanisms. Metab. Brain Dis. 26: 79–85.  
13. Monekosso, 
G.L., 
W.G. 
Anan 
& 
P.H. 
Ashby. 
1964. 
TherapeuticeffectofvitaminBcomplexonanataxicsyndromein 
western 
Nigeria. 
Trans. R. Soc. Trop. Med. Hyg. 58: 432–436.  
14. Tylleskar, T., M. Banea, N. Bikangi, et al. 1991. Epidemiological evidence from 
Zaire 
for 
a 
dietary 
etiology 
of 
Konzo, 
anuppermotorneuronediseasefoundinAfrica.Bull.World Health Organ. 69: 581–
589.  
15. Plant, G.T., A.T. Mtanda, G.B. Arden, et al. 1997. An epidemic of optic 
neuropathy in Tanzania: characterization of the visual disorder and associated 
peripheral neuropathy. J. Neurol. Sci. 145: 127–140.  

16. Dalmar, A.A., K.E. Hodson & G.T. Plant. 2011. Epidemic optic neuropathy is 
evident in the Somalian population. J. Neuroophthalmol. 31: 127–130.  
17. Macias-Matos, C., A. Rodriguez-Ojea, N. Chi, et al. 1996. Biochemical evidence 
of 
thiamine 
depletion 
during 
the 
Cubanneuropathicepidemic,1992–
1993.Am.J.Clin. Nutr. 64: 347–353. 
18. Crook MA, Sriram K. Thiamine deficiency: the importance of recognition and 
prompt 
management. 
Nutrition 
(2014) 
30(7–8):953–4. 
doi:10.1016/j. 
nut.2014.03.003  
19. Frank LL. Thiamine in clinical practice. JPEN J Parenter Enteral Nutr (2015) 
39(5):503–20. doi:10.1177/0148607114565245 10 
 
 

PART –E 
BUDGET 
I. Total Budget: 2,50,000 bdt (Two lacs and fifty thousand taka only) 
II. Detailed Budget: 
1. Personnel cost: Not Applicable. 
2. Field Expenses/ Laboratory Costs: 1,50,000. 
3. Supplies and Materials: 
4. Patient Cost (if applicable): Transport fee 55,000. 
5. Travel cost (Internal travel cost only) : 5000. 
6. Transportation of Goods: Not Applicable. 
7. Office Stationary: Internet  5000 
                                 Stationary 5000 
                                Photocopy  5000. 
8. Data Processing/ Computer Charges: 15,000. 
9. Printing and Reproduction: 10,000. 
10. Contractual Services (other than manpower): Not Applicable. 
11. Administrative Overhead: Not Applicable. 
12. Miscellaneous: Not Applicable. 
 
 
 
 
 

PART –F 
Informed Consent Form 
Efficacy of Thiamine in Patients with Clinically Suspected Dry 
Beriberi: An Open Labeled Hospital Based Study. 
 
After being fully informed about the objectives ,consequences of the study 
and any right to withdraw myself from the study at any time for any purpose 
what so ever, I am…………………………………………Here by giving 
consent to participate in the study conducted by Dr.Nayema Masrura, 
(Neurology) thesis part student, CMCH.  
 
I fully recognize that my participation in this study will generate valuable 
medical information that might be used for the interest of patients in future.  
 
In this research if any adverse effects of drugs are found investigators will 
take immediate measures for treatment.  
 
I shall try my best comply with the instruction given by the investigator 
throughout the whole period of study. 
 
 
 
 
 
Signature/Thumb impression of the 
patient’s guardian  
Date………………  
 
 
 
Signature/Thumb impression of the  
Subject  
Date………………  
 
 
 
Signature/Thumb impression of the  
Investigator  
Date………………  
 
 
 
Signature/Thumb impression of the  
Witness  
Date………………  

PATIENT INFORMATION  SHEET 
Efficacy of Thiamine in  Patients with Clinically Suspected Dry 
Beriberi: An Open Labeled Hospital Based Study. 
Introduction: 
Beriberi is a severe form of Thiamine (vitamin B1) deficiency. Historically it is prevalent 
in countries which use polished rice as staple food. Disease is manifested by muscle 
weakness, difficulty in walking, leg swelling, heart failure, unusual tiredness, memory 
loss, anorexia, nausea etc. Diets rich in Thiamine are pulse, beef, liver, dried milk, nuts, 
oats, oranges, pork, eggs, seeds, legumes, peas and yeast. Foods are also fortified with 
thiamine. Some foods that are often fortified with B1 are rice, pasta, breads, cereals and 
flour. 
Procedure for objective:  
 
This research will be conducted by the department of Neurology, CMCH. If you are 
agreed to take part in this research, then the researcher doctor will ask you some relevant 
questions.  
Risk of the research: no known risk. 
Advantages for participate in the research: 
If you participate in the research, then you may be benefited directly. You will get the 
chance of proper diagnosis and treatment. This research will help the Bangladeshi doctors 
to know more about the disease. This research may be useful for a large number of 
people of the country.  
Expenditure:  
For participation in this research you have no expense or payment. 
Confidentiality:  
Confidentiality will be strictly maintained for all information during and after the 
research. You will be given an ID number for follow up. All of your information will be 
kept under lock and key in the office file cabinet. Personal information will not be used 
for any analysis, research or publication and will not be revealed to anyone except the 
researchers. As a result none can know your personal information.  
 
 

Voluntary participation:  
Participation in the research is completely voluntary. You can refuse to participate in the 
research or withdraw yourself from the research any time after participation. Signing in 
this consent form will not hamper your any legal rights. 
Queries: If any query, contact with the researcher Dr. Nayema Masrura, Mobile 
01707743838, Department of Neurology, CMCH. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

PART-G 
CASE RECORD FORM 
Title: Efficacy of Thiamine in Patients with Clinically Suspected 
Dry Beriberi: An Open Labeled Hospital Based Study. 
ID no:                   Ward No:                      Bed no:                          Reg. No: 
Date of admission:                                    Date of Discharge: 
Date of inclusion in study: 
Contact No:                                                Address: 
Particulars of the Patient: 
1.  Name: 
2. Age (in years):  
3. Sex:  Male=1/Female=2.  
4. Religion:  Muslim=1/ Hindu=2/Buddist=3 / Christian=3                            
5. Marital Status:  Married=1/ Unmarried=2/ widow=3/divorced=4.  
6. Residence: urban=1/ semi urban=2/rural=3/others=4(specify).  
7. Education: 
8. Occupation:  
9. Monthly Income:   
10. Food Habit:  
a) Rice eaten: Polished un-boiled=1/polished boiled=2 
b) Washing before cooking:  ………….times    
c) Discarding excess water after cooking: no=1/yes=2.  
d) No of meals per day:  
 
 

 
e) Contents of major meals: 
Breakfast 
Snacks 
Lunch 
Afternoon Snacks 
Dinner 
 
 
 
 
 
 
f) Anti-thiamine food intake: Betel nut/ tea/ fermented fish/shell fish.   
                                                 ………..min after major meal,……..times per day 
 
11. Alcohol intake: 
     Duration……….years, Amount:…………./day 
                 current alcohol user=1/ former alcohol user=2/ never alcohol user=3. 
12. Other associated conditions (if any):  
GIT 
surgery/ 
Chr. 
Diarrhoea/ 
Chr. 
Vomitting/Renal 
disease/ 
cancer/ 
pregnancy/others (specify): 
13. No of childbirth (in females): 
Time of last childbirth:  
Duration of Lactation: 
12. Presenting Symptoms: 
      12.1) Limb Weakness:  Upper limb/ lower limb/ both.        Duration:………..days  
               12.2) Leg swelling:  yes/ no. Duration…………..days 
                      Nil=0, Mild=+, moderate=++, severe=+++ 

              12.3) Sensory Impairment (pain, tingling, numbness): yes/ no. Duration: 
……………. Days. 
        12.4) anorexia , nausea :  yes/ no. Duration: ……………. Days. 
        12.5) Muscle cramp: no/mild/moderate/severe. Duration: ……………. Days. 
         12.6) other symptoms (specify):  Duration: ……………. Days. 
13. Physical Examination: 
    13.1) Height: …………., weight:……………..Kg,    BMI (weight/height2): 
 
      13.2) Mid Upper Arm Circumference(MUAC):………………cm 
 
      13.3) Anaemia: Absent/ Present. 
                    13.4) muscle power (MMRC Grading): 
Upper Limb     
            Lower Limb 
Proximal: 
Proximal: 
Distal: 
Distal: 
 
                          13.5) deep tendon reflexes: normal =0, Diminished=1, Absent=2 
 
Biceps 
Triceps 
Supinator 
Knee 
Ankle 
Planter 
Right 
 
 
 
 
 
 
Left 
 
 
 
 
 
 
                       
                         13.6) Squat test: negative=0/ positive=1.  
                         13.7) Sensory Impairment: Normal =0, Diminished=1,Absent=2 
                   
pain 
touch 
temperature 
Position sense 
vibration 
Upper limb 
 
 
 
 
 
Lower limb 
 
 
 
 
 
        
        13.8) 
neuropathic 
Pain 
(VAS 
Score): 
nil=0/mild=1/moderate=2/sever=3.  

       13.8) Pulse : ………./min                                                                                   
       13.9) BP: ……………..m m hg                                       
       13.10) Resp Rate: ………/min 
       13.11) JVP: normal/ Raised 
       13.12) other :if present,(specify) 
14. Investigations: 
14.1) CBC: 
14.2) Urine R/E: 
14.3) Serum creatinine:                                            14.4Serum Electrolytes: 
                          14.5) LFT: a) SGPT:                                            b) SGOT   
                                           c) PT:                                                  d) Serum Albumin:        
                          14.6) OGTT   a) FBS :                                  b) 2 hr after 75 gm glucose: 
                          14.7) HbA1C: 
                          14.8) TSH 
                          14.9) serum B12 assay: 
                          14.10) CXR PA view 

               14.11) ECG 
               14.12) Echocardiography: 
               14.13) CSF Study: 
               14.14) NCS (Nerve conduction study): 
                 
 
 
 
 
 
 
 

15. Therapeutic Response: 
                       
Parameters 
 Assessment 
Before 
treatment (A 0) 
Date: 
 Assessment  
After 1 wk   
(A 1) 
Date: 
Assessment  
After 6 wk 
(A 2) 
Date: 
Assessment After 
12 wk 
(A 3) 
Date: 
A)Leg Swelling 
 
 
 
 
 
B)Muscle Power 
(MMRC grading) 
Upper Limb 
Lower Limb 
 
 
 
 
C)Deep Tendon 
Reflexes 
Upper Limb 
Lower Limb 
 
 
 
 
D)Squat Test 
 
 
 
 
E)Sensory 
impairment 
 
 
 
 
 Pain  
 
 
 
 
 
touch 
 
 
 
 
 
position 
 
 
 
 
Vibration 
 
 
 
 
Tingling , 
Numbness 
 
 
 
 
Hyperaesthesia 
(VAS score) 
 
 
 
 
F) Muscle cramp 
(VAS score) 
 
 
 
 
H) Overall 
Neuropathy 
Limitation Scale 
(ONLS) 
 
Arm 
Score………….. 
Leg 
Score…………… 
Total: 
Arm 
Score………….. 
Leg 
Score…………… 
Total: 
Arm 
Score………….. 
Leg 
Score…………… 
Total: 
Arm 
Score………….. 
Leg 
Score…………… 
Total: 

Medical Research Council (MRC) Scale for Muscle Power 
 
 
 
Muscle tested for Power 
Upper limb 
Lower limb 
Shoulder abduction 
Shoulder adduction 
Elbow flexion 
Elbow extension 
Supination 
Pronation 
Finger abduction & adduction 
Thumb opposition, abduction & adduction 
 
Hip flexion 
Hip extension 
Knee flexion 
Knee extension 
Foot dorsiflexion 
Foot planter flexion 
Great toe extension 
Great toe flexion 
 
 
                    
 
0 
no muscle contraction visible 
 
1 
Flicker of contraction but no movement 
 
2 
Joint movement when effect of gravity eliminated 
 
3 
Movement against gravity but not against examiner’s resistance 
 
4 
Movement against resistance but weaker than normal 
 
5 
Normal power 
 

 
 
                       
Visual Analogue Scale (VAS) for pain 
 
 
 
Neuropathic pain/Hyperaesthesia 
VAS Score 
Nil=0 
0 
Mild=1 
1-3 
Moderate=2 
4-6 
Severe=3 
7-10 
Overall Neuropathy Limitations Scale (ONLS) 

Instructions: The examiner should question and observe the patient in order to determine 
the answers to the following questions. Note should be made of any other disorder other 
than peripheral neuropathy which limits function at the foot of the page. 
ARM SCALE: 
 
Does the patient have any symptoms in their hands or arms, eg tingling, numbness 
or weakness?       Yes/ No.                                                                                             
                                            (if "no", please go to "legs" section) 
 
Is the patient affected in their ability to: Not affected /Affected but not prevented/ 
Prevented 
 
1. Wash and brush their hair 
2. Turn a key in a lock 
3. Use a knife and fork together (or spoon, if knife and fork not used) 
4. Do or undo buttons or zips 
5. Dress the upper part of their body excluding buttons or zips 
6. If all these functions are prevented can the patient make purposeful movements 
with their bands or arms? 
Arm Grade 
0= Normal 
1= Minor symptoms in one or both arms but not affecting any of the functions listed 
2= Disability in one or both arms affecting but not preventing any of the functions listed 
3= Disability in one or both arms preventing at least one but not all functions listed 
4= Disability in both arms preventing all functions listed but purposeful movement still 
possible 
5= Disability in both arms preventing all purposeful movements 
 
Arm SCORE= 
LEG SCALE 
 

Does the patient have difficulty running or climbing stairs? 
Does the patient have difficulty with walking? 
Does their gait look abnormal? 
How do they mobilise for about 10 metres (ie 33 feet)? 
         Without aid 
         With one stick or crutch or holding to someone's arm 
         With two sticks or crutches or one stick or crutch holding onto someone's arm or 
frame 
         With a wheelchair 
If they use a wheelchair, can they stand and walk 1 metre with the help of one person? 
If they cannot walk as above are they able to make some purposeful movements of their 
legs, eg reposition legs in bed? 
 
Does the patient use ankle foot orthoses/braces? (if yes,please circle)  right/left 
 
Leg grade 
 
0= Walking/climbing stairs/running not affected 
1= Walking/climbing stairs/running is affected, but gait does not look abnormal 
2= Walks independently but gait looks abnormal 
3= Requires unilateral support to walk 10 metres (stick, single crutch, one arm) 
4= Requires bilateral support to walk 10 metres (sticks, crutches, crutch and arm,frame) 
5= Requires wheelchair to travel 10 metres but able to stand and walk 1 metre with the 
help of one person 
6= Restricted to wheelchair, unable to stand and walk 1 metre with the help of one 
person, but able to make some purposeful leg movements 
7= Restricted to wheelchair or bed most of the day, unable to make any purposeful 
movements of the legs 
Is there any disorder, other than peripheral neuropathy, which affects the above 
functions: Yes / No 
If yes please describe: 
 
Leg SCORE= 
TOTAL SCORE=       (Arm SCORE)    +        (Leg SCORE) 
Overall Neuropathy Limitation Scale = arm scale (range 0 to 5) + leg scale (range 0 to 7); 
range: 0 (no disability) to 12 (maximum disability).