Before the modern neuroimaging era, treatment decisions in neurology were based on findings obtained almost solely from the history and clinical examination of the patient. In spite of the development of computed tomography, magnetic resonance imaging (MRI) scans, and other sophisticated neuroimaging methods, the clinical recognition of signs that may be associated with intracranial neoplasms (brain tumor) is of importance to practice. Simple, precise, and practical clinical tests are particularly advantageous, as some tumors may remain unnoticed for many years.1 Considering that early detection and resection of brain tumors may be curative or may significantly improve prognosis, clinicians must be alert to promptly recognize subtle motor deficits that often accompany these tumors.1
Recognition of subtle motor deficits, minimal reductions in strength that may not be perceived by the patient but that manifest as slight difficulty in routine activities,2 can alert the clinician to the need to proceed to the appropriate diagnostic evaluation. The present study sought to determine the sensitivity,3 specificity,3 and positive and negative predictive values3 of 13 tests used to detect subtle motor deficits as early indicators of monohemispheric brain lesions. To the best of our knowledge, such battery of tests has not been studied simultaneously in the same patients with unilateral intracranial tumors.
This study was performed at the outpatient clinic, neurosurgery department, at the National Cancer Institute in Rio de Janeiro, Brazil. The study was approved by the National Cancer Institute Ethics Committee (# 007/06), and all participants signed an informed consent. Sixty patients with identified monohemispheric cerebral tumors (mean age = 46 ± 28 years; range = 18-74 years) were evaluated. Thirty-two (53%) were female and 58 (97%) were right handed. All had a history of at least 1 month of headaches and/or seizures, while none complained of weaknesses. Thirty-nine (65%) had a right hemisphere cerebral tumor and 21 (35%) had a left hemisphere cerebral tumor. Histological diagnosis and tumor locations for the 60 patients are given in Table 1. A control group consisting of 30 individuals (mean age = 53.5 ± 21.5 years; range = 32-75 years) referred with complaints of vertigo, migraine, or seizures, but in whom no tumor had been identified was also evaluated. Twenty (67%) were female and 26 (87%) were right handed.
All participants from both groups underwent brain MRI. The inclusion criteria were unilateral cerebral tumor confirmed by MRI, no obvious motor deficits, and Mini-Mental State Examination (MMSE)4 with score greater than 25 points. Patients were excluded if they had nonneurological disorders that hindered neurological assessment, aphasia, movement disorders, a marked midline shift associated with a focal brain tumor, consciousness or cognitive impairments that could have affected their cooperation with the neurological examination, or brainstem, cerebellar, or bilateral cerebral tumors. Initially, 94 patients were prospectively enrolled. Four did not meet the inclusion criteria; of these, 2 presented with bihemispheric brain tumors noticed only when the MRI scans were reviewed, 1 declined to sign the informed consent, and 1 did not attain the required 25 points for the MMSE.4
Experimental Protocol and Data Collection
Patients and controls underwent a comprehensive neurological examination and referral to a physical therapist (E.T.M.) who performed MMSE4 and 13 clinical tests. The physical therapist was blinded to which subjects had brain tumors and was blind to any clinical or imaging data. A list of the 13 clinical tests, the eliciting maneuvers, and the associated sign indicating a positive test are given in Table 2. For each test, we determined the sensitivity (the true positive rate), defined as the ability of the test to elicit a positive sign when the target condition is really present. We also determined the specificity, defined as the probability of an incorrect positive result in those who do not have the target condition. We determined the positive and negative predictive values that estimate the likelihood that a person who tests positively actually has the disease or is actually disease free, respectively. The Digit Quinti Rolling Sign was not performed in all patients because it was developed during the testing phase of the study. Finally, the Kappa index was used to assess concordance among measures.
The histopathologic diagnosis and affected lobules of the tumors identified in the 60 patients are given in Table 1. Sensitivity, specificity, and positive and negative predictive values (with 95% confidence intervals [CI]) are given in Table 3. The most sensitive tests (and 95% CI) were the Digit Quinti Sign (DQS), 0.51 (0.41-0.61); the Pronator Drifting Test (PDT), 0.41 (0.31-0.51); the Finger Rolling Test (FiRT), 0.41 (0.31-0.51); the Souques Interosseous Sign (SIS), 0.23 (0.14-0.32); and the Foot Tapping Test (FTT), 0.23 (0.14-0.32). The tests with greatest specificity were DQS, 0.70 (0.61-0.79); PDT, 0.96 (0.92-0.99); the Forearm Rolling Test (FRT), 0.93 (0.88-0.98); SIS, 0.80 (0.72-0.88); and FTT, 0.93 (0.88-0.98). The agreement measurement among the 3 most sensitive signs was 21%. The Kappa index for the 3 most sensitive tests indicated no significant concordance.
When motor system dysfunction is present, muscular weakness is the most common manifestation of this dysfunction. Several authors have described tests to detect mild arm dysfunctions indicative of brain lesions,8,9,10 but only a few have assessed the sensitivity and specificity of these tests.2,8 The aim of our study was to identify the most useful of 13 clinical tests for detection of monohemispheric cerebral lesion. The DQS, PDT, and FiRT were the most sensitive tests, while the DQS, PDT, and FRT had the greatest specificity.
The DQS, described by Alter in 1973,10 showed the highest sensitivity among the 13 tests we evaluated; a positive sign was present in 31 (52%) of our patients. Alter10 himself questioned whether the DQS was just an expression or the “phénomène des interosseux” described more than a century ago by the French neurologist Souques.12 In our study, the SIS was present in 14 (23%) of our patients and was contralateral to the tumor in 8 of these. In all but one, the SIS was concordant with the DQS. In spite of this concordance, we cannot consider the DQS as an isolated sign, more sensitive than the SIS, or related to it.
The PDT described by Babinski13 in 1907 is considered one of the most sensitive signs in identifying subtle motor deficits in the upper extremities. Weaver2 studied 50 patients with subtle brachial monoparesis (not taking into account the origin of the disease or chronicity of the disease) and found that the PDT was present in 76% of the cases. Sawyer et al8 studied 62 individuals who also had subtle upper extremity motor deficits, most of them being poststroke patients and 6 having cerebral tumors, and they found that the PDT was present in 79% of patients. On the other hand, Anderson et al20 evaluated 46 individuals without obvious motor deficit, with cerebral lesion from different etiologies. They observed the PDT in only 22% of the patients and observed none in the 19 control subjects without cerebral lesion. In the earlier mentioned studies, patients had focal cerebral lesions coming from different origins, the majority having had cerebral infarct. Among our subjects, the PDT was present in 25 (42%), and only 1 (3.3%) individual from the control group showed an asymmetric response.
During the 1990s, 2 tests were described to detect mild upper extremity paresis. Sawyer et al8 observed the FRT in 62 patients with unilateral acute and chronic brain lesions and in none of the 20 controls with normal imaging tests. Anderson et al20 found the FRT to be positive in 24% of 46 patients with subtle motor deficits and unilateral cerebral lesion. In our study, the FRT was asymmetric in 17% of our patients and none of the controls. It is noteworthy that all controls were right-hand dominant and showed symmetry on this maneuver, suggesting that dominance and manual skills do not seem to influence the responses. Two years after the original description of the FRT, Yamamoto9 compared the FiRT with the FRT in 28 patients with unilateral cerebral lesion and found it to be present in 61% of the subjects although the FRT was present in only 21%. Our results confirmed Yamamoto's finding as we observed the FRT in 17% and the FiRT in 41% of the patients.
Based on the knowledge that the corticospinal tract produces facilitatory postsynaptic action potentials predominantly for the control of fine, discrete movements of the fingers,21 and that the digit quinti has less cortical representation than the forearm or index finger,8 we developed the Digit Quinti Rolling Sign.16 If discrete pyramidal tract lesions are associated with subtle paresis of the hand, then it is more likely to manifest deficits in the fifth digit than any other. Unfortunately, our patients presented great difficulty in correctly performing the rolling movements of only the digit quinti, showing a tendency to move the entire hand. This might have contributed to the unexpected very low sensitivity of the test. We believe that more patients must be tested before reaching a definite conclusion regarding this maneuver.
Subtle motor deficits can also be measured by evaluating repetitive rapid movements and comparing the maximum frequency of uninterrupted beatings of the index finger or strikes of the forefoot while the heel remains fixed.14 Miller and Johnson17 performed a comparative study of the Babisnki Sign versus the FTT for diagnosis of pyramidal tract dysfunction. Despite considerable criticism for making comparisons between a reflex response and the ability to perform a voluntary motor activity,22 the authors considered the FTT to be advantageous. In our study, the FTT was positive in only 14 (23%) of our 60 patients.
Despite the fact that positive results for the Spasticity of Conjugate Gaze,5 Platysma Sign,6,7 Babinski Sign,18 Chaddock Sign,19 and Mayer Sign15 all indicate pyramidal tract dysfunction, they presented low indices of sensitivity (0.01, 0.01, 0.08, 0.03, and 0.06, respectively) for monohemispheric brain tumors.
The limited number of recruited patients is a limiting factor of this study and may have contributed to the low specificity and sensitivity results for some of the tests we included. Furthermore, differences among patients in the tumor location may have contributed to the lack of positive findings in some tests. It is possible that a combination of tests may improve sensitivity and provide a more comprehensive battery of clinical tests to identify the need for imaging.
Our results indicate that the DQS, PDT, and FiRT are the most sensitive tests to detect the subtle motor deficits associated with monohemispheric brain tumors. Clinicians should consider using tests to identify subtle motor deficits as complementary items in their neurological examination. These tests are simple to perform and easy to interpret; their presence may indicate the need for neuroimaging for a definitive diagnosis.
The authors are grateful to Péricles de A. Maranhão Neto for technical assistance and help with the English language.
1. Rupp C, Riggs HE, Hogan HW, Moulton JAL. Primary brain tumours in patients over age 60. Neurology. 1953; 3:586–590.
2. Weaver DF. A clinical examination technique for mild upper motor neuron paresis of the arm. Neurology. 2000; 54:531–532.
3. Portney GL, Watkins PM. Foundations of Clinical Research-–Applications to Practice. 3rd ed. New Jersey: Pearson Education Inc; 2009:620–626.
4. Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12:189–198.
5. Cogan DG. Neurologic significance of lateral conjugate deviation of eyes on forced closure of lids. Arch Ophthalmol. 1948; 9:37.
6. van Gijn J. The Babinski Sign-—A Centenary. Heidelberglaan, Utrech: Universiteit Utrecht; 1996.
7. Fidias E, Leon-Sarmiento FE, Prada LJ, Torres-Hillera M. The first sign of Babinski. Neurology. 2002; 59:1067.
8. Sawyer RN, Hanna JP, Ruff RL, Leigh RJ. Asymmetry of forearm rolling as a sign of unilateral cerebral dysfunction. Neurology. 1993; 43:1596–1598.
9. Yamamoto T. Forearm-rolling test [Correspondence]. Neurology. 1995; 45:2299.
10. Alter M. The Quinti digiti sign of mild hemiparesis. Neurology. 1973; 23:503–505.
11. Monrad-Krohn GH. Exploración Clínica del Sistema Nervioso. Barcelona, Spain: Editorial Labor SA; 1967:157.
12. A-A Souques. Sur le “phénomène des interosseux” de la main ou “phénomène des doigt” dans l'hémiplégie organique. Bulletins et mémoires de la Société médicale des hôpitaux de Paris. 1907; 24:677.
13. Babinski J. De La pronation de La main dans l'hémiplégie organique. Revue Neurologique. 1907; 15:755.
14. DeJong's. The neurological examination. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.
15. Wartemberg R. The examination of reflexes a simplification. Chicago, IL: The Year Book Publishers Inc; 1945.
16. Maranhão-Filho PA, Maranhão ET. A evolucão do Exame Neurológico e alguns sinais descritos a partir do século XX. Semiologia neurológica. Rev Bras Neurol. 2007; 43:5–11 (in Portuguese).
17. Miller TM, Johnston SC. Should the Babinski sign be part of the routine neurologic examination? Neurology. 2005; 65:1165–1168.
18. Babinski J. Sur le réflexe cutané plantaire dans certains affections organiques du système nerveux central. C R Soc Biol (Paris). 1896; 48:207–208.
19. Chaddock CG. The external malleolar sign. Interstate Med J. 1911; 13:1026–1038.
20. Anderson NE, Mason DF, Fink JN, Bergin PS, Charleston AJ, Gamble GD. Detection of focal cerebral hemisphere lesions using the neurological examination. J Neurol Neurosurg Psychiatry. 2005; 76:545–549.
21. Davidoff RA. The pyramidal tract. Neurology. 1990; 40:332–339.
22. Landau WM. Plantar reflex amusement. Misuse, ruse, disuse, and abuse. Neurology. 2005; 65:1150–1151.
brain tumor; intracranial neoplasm; pyramidal tract lesion; subtle motor sign