Fujii, et al. (2002). Olfactory dysfunction in patients with head trauma.

[Wise Young]

Fujii M, Fukazawa K, Takayasu S and Sakagami M (2002). Olfactory dysfunction in patients with head trauma. Auris Nasus Larynx. 29 (1): 35-40. Summary: OBJECTIVE: There are few reports about following up olfactory acuity of the patients who have post-traumatic olfactory dysfunction. In this study, we studied about patients with post-traumatic olfactory dysfunction for a short period under a treatment. METHODS: The olfactory function of 27 patients with head trauma was studied. The olfactory acuities of all the patients were examined using olfactory tests before the treatment, and 18 patients were examined again after the treatment. Olfactory functions were evaluated in 26 patients by T&T olfactometry and in 27 patients by Alinamin test. All of the patients were treated with a local injection of suspended steroid solution into the nasal mucosa [J Otolaryngol Jpn 102 (1999) 1175]. RESULTS: Before the treatment, 16 patients (61.5%) presented anosmia, five patients (19.2%) presented severe hyposmia, three patients (11.5%) presented moderate hyposmia, and two patients (7.7%) presented mild hyposmia. Eighteen cases (69.2%) were negative for the Alinamin test and eight cases (30.8%) were positive. The improvement rates of recognition and detection thresholds by T&T olfactometry were 35.3 and 23.5%, respectively. CONCLUSION: Olfactory dysfunction caused by head trauma can be recovered to a limited degree in some cases by the local injection of steroid within the relatively short period from the start of the therapy. Department of Otorhinolaryngology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. megumi@hyo-med.ac.jp

[Wise Young]

Interestingly, this study suggests that patients effort must be taken into account in evaluating anosmia evaluation:

1. Green P and Iverson GL (2001). Effects of injury severity and cognitive exaggeration on olfactory deficits in head injury compensation claims. NeuroRehabilitation. 16 (4): 237-43. Summary: The purpose of this study was to examine the relationship between exaggeration and scores on a test of olfactory discrimination in patients being assessed in connection with a claim for financial benefits. Participants were 448 patients referred to a private practice in Edmonton, Alberta, Canada for psychological or neuropsychological assessment, related to evaluation of impairment and disability resulting from a work-related or non-work related accident. All patients were involved in some form of compensation claim at the time of their evaluation. All patients completed two tests designed to detect exaggerated cognitive deficits, the Computerized Assessment of Response Bias (CARB) and the Word Memory Test (WMT) as part of their evaluation. The diagnostic groups included 322 head injury cases, varying from very minor to very severe. Normative data for the smell test were derived from 126 patients with orthopedic injuries who passed both the CARB and the WMT. Patients with more severe traumatic brain injuries were 10-12 times more likely to have olfactory deficits than persons with trivial to mild head injuries. In a subgroup of patients who failed either the CARB or the WMT, there was no relationship between injury severity and total scores on the smell test. Therefore, the dose-response relationship between brain injury severity and olfactory deficits is severely attenuated when patients who are probably exaggerating their cognitive deficits are included in the analyses. Those patients with trivial to mild head injuries who demonstrated adequate effort on both the CARB and the WMT were no more likely to show olfactory deficits than the non-head-injured orthopedic control subjects. Therefore, anosmia following mild traumatic brain injury should not be concluded from self-reports or from tests of smell unless tests of effort have been passed. Effort should also be controlled in group studies of olfaction. Private Practice with Neurobehavioural Associates, Edmonton, Alberta, Canada.

[Wise Young]

Another study suggests that MRI of the olfactory bulb is a useful predictor:
1. Yousem DM, Geckle RJ, Bilker WB, Kroger H and Doty RL (1999). Posttraumatic smell loss: relationship of psychophysical tests and volumes of the olfactory bulbs and tracts and the temporal lobes. Acad Radiol. 6 (5): 264-72. Summary: RATIONALE AND OBJECTIVES: The purpose of this study was to define the primary sites of injury in patients with posttraumatic anosmia and hyposmia with magnetic resonance (MR) imaging and to determine if these sites correlated with the results of psychophysical olfactory tests. MATERIALS AND METHODS: Thirty-six patients with subjective loss in olfaction after head trauma underwent volumetric MR studies of the olfactory bulbs and tracts and temporal lobes. Pearson correlations were computed between olfactory bulb and tract and temporal lobe volumes and the patients' scores on tests of odor identification (including the University of Pennsylvania Smell Identification Test [UPSIT]), detection, and memory. Analysis of variance was used to compare volumes of the control subjects and the posttraumatic patients. RESULTS: The olfactory bulbs and tracts (32 [89%] of 36 patients), the subfrontal lobes (22 [61%] of 36 patients), and the temporal lobes (11 [31%] of 36 patients) showed the highest incidence of posttraumatic encephalomalacia. Left olfactory bulb and tract volumes showed a statistically significant correlation with left and total UPSIT scores. A statistically significant difference (P < .001) was found in the right and left olfactory bulb and tract volumes between anosmic and hyposmic patients and between posttraumatic patients and control subjects. CONCLUSION: Olfactory bulb and tract damage may correlate with deficits in odor identification. Olfactory bulb and tract and frontal lobe encephalomalacia coexist in many patients. Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, USA.

[Wise Young]

1. Geisler MW, Schlotfeldt CR, Middleton CB, Dulay MF and Murphy C (1999). Traumatic brain injury assessed with olfactory event-related brain potentials. J Clin Neurophysiol. 16 (1): 77-86. Summary: Olfactory event-related potentials (OERPs) were evaluated to develop an objective, quantitative assessment of sensory and cognitive olfactory loss following traumatic brain injury (TBI). Subjects included 25 TBI patients and 25 age/gender-matched healthy controls. Following standard clinical evaluation of smell function, TBI patients were divided into three groups: 12 anosmics (loss of smell), 6 hyposmics (reduced smell), and 7 normosmics (normal smell). Cognitive ability was assessed using the Trail Making Test (A and B). OERPs were recorded monopolarly from midline electrode sites using an amyl acetate stimulus with a 60-second interstimulus interval; subjects estimated the magnitude of each odor stimulus. Anosmic TBI patients were also tested with OERPs using ammonia to ensure trigeminal nerve function. Amyl acetate OERPs demonstrated that the sensory N1 and P2 amplitudes and the cognitive P3 amplitudes were absent in the anosmic TBI patients and greatly reduced in the hyposmic and normosmic TBI patients compared to healthy controls. The trigeminal OERPs from the anosmic TBI patients were within normal limits, indicating that the primary olfactory deficits were objectively measured with OERPs. The relationship between the OERPs and neuropsychologic test performance supports the cognitive loss associated with TBI. The present study lends support to the utility of OERPs as an objective tool for measuring sensory and cognitive loss after traumatic brain injury. University of California Medical Center, San Diego, USA.

[Wise Young]

Sullivan TE, Warm JS, Schefft BK, Dember WN, O'Dell MW and Peterson SJ (1998). Effects of olfactory stimulation on the vigilance performance of individuals with brain injury. J Clin Exp Neuropsychol. 20 (2): 227-36. Summary: Observers with brain injury and control participants performed a vigilance task during which they received periodic whiffs of unscented air or air scented with peppermint. Under both fragrance conditions, controls reduced the frequency of commissive errors (false alarms) over the course of the vigil, an adaptive strategy given the low probability of signals employed (0.04). The false alarm rate of observers with brain injury increased precipitously toward the end of the vigil in the unscented air condition. However, exposure to the scent of peppermint rendered the false alarm scores of observers with brain injury similar to that of controls, a result which is consistent with evidence that olfactory stimulation activates brain areas vital for planning and judgment. University of Cincinnati, USA. sullt0@chmcc.org

[Wise Young]

Levy LM, Henkin RI, Hutter A, Lin CS and Schellinger D (1998). Mapping brain activation to odorants in patients with smell loss by functional MRI. J Comput Assist Tomogr. 22 (1): 96-103. Summary: PURPOSE: Our goal was to use functional MRI (fMRI) to develop an objective, noninvasive technique by which patients with smell loss can be identified, their abnormalities quantitated, their results compared with findings in normal subjects, and visual representation of their CNS pathology obtained. METHOD: Functional MR brain scans were obtained in eight patients with hyposmia in response to three olfactory stimuli (pyridine, menthone, amyl acetate) in three coronal brain sections selected from anterior to posterior temporal brain regions using multislice FLASH MRI. Results were compared with similar studies performed in 17 normal subjects. Activation images were derived using correlation analysis, and ratios of area of brain activated to total brain area were obtained. RESULTS: Brain activation to each stimulus was lower in each section in patients compared with normal subjects and reached statistical significance for mean activation for each odor and in six of the nine individual sections studied. Activation in patients was found in regions previously associated with CNS processing of olfactory stimuli in normal subjects, but activation in patients was much less, particularly in inferior frontal and cingulate gyral regions of frontal cortex and in regions of medial and posterior temporal cortex. CONCLUSION: These results demonstrate quantitative CNS changes in smell function in response to olfactory stimuli in patients with hyposmia, demonstrate a novel, objective method by which these patients can be identified, and provide maps of the CNS changes associated with their smell loss. Department of Radiology, Georgetown University Hospital, Washington, D.C., USA.

[Wise Young]

In this 1997 study, Doty, et al. examined 268 patients with head injury and showed 67% had anosmia, 20% had hyposmia, and 10% were normal. Interestingly, olfactory bulb atrophy was noted in males but not females. Patients who complained of anosmia generally had anosmia and rarely recovered to normal.


Doty RL, Yousem DM, Pham LT, Kreshak AA, Geckle R and Lee WW (1997). Olfactory dysfunction in patients with head trauma. Arch Neurol. 54 (9): 1131-40. Summary: BACKGROUND: The ability to smell is commonly altered by head trauma (HT). However, the nature, prevalence, prognosis, and etiology of such alterations are poorly understood. OBJECTIVES: To quantitatively determine the degree of olfactory function in patients with HT-related chemosensory complaints and to examine the influences of age, sex, HT severity, time since HT, and other variables on such function. Also, to use quantitative magnetic resonance imaging (MRI) to establish whether and to what degree damage to the olfactory bulbs and tracts, frontal lobes, and temporal lobes occurs. PATIENTS AND METHODS: Two hundred sixty-eight patients with HT from the University of Pennsylvania Smell and Taste Center, Philadelphia, were administered a quantitative odor identification test, a depression inventory, and a medical history questionnaire; 66 were retested after individual test-retest periods ranging from 1 month to 13 years. The volume of olfactory-related brain structures was determined in 15 patients and 15 controls using MRI. RESULTS: One hundred seventy-nine patients (66.8%) had anosmia, 55 (20.5%) had microsmia, and 34 (12.7%) had normosmia. Frontal impacts produced less dysfunction than back or side impacts. Of the 66 retested patients, 24 (36%) improved slightly, 30 (45%) had no change, and 12 (18%) worsened; only 3 patients, none of whom initially had anosmia, regained normal olfactory function. Trauma severity was related to olfactory test scores in patients with microsmia. Parosmia prevalence decreased from 41.1% to 15.4% over an 8-year posttrauma period. Olfactory bulb and tract volumes of male, but not female, patients with HT were greatly reduced relative to volumes of controls. CONCLUSIONS: Patients complaining of HT-related olfactory dysfunction typically have anosmia and rarely regain normal olfactory ability, parosmia prevalence decreases over time in such patients, and damage to olfaction-related brain structures can be observed in most such patients using an appropriate MRI protocol. Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Medical Center, Philadelphia, USA.

[Wise Young]

The authors report very high rates (88%) of injury to olfactory bulbs or tracts after head injury.
Yousem DM, Geckle RJ, Bilker WB, McKeown DA and Doty RL (1996). Posttraumatic olfactory dysfunction: MR and clinical evaluation. AJNR Am J Neuroradiol. 17 (6): 1171-9. Summary: PURPOSE: To evaluate the sites of injury in patients with posttraumatic olfactory deficits and to compare damage with findings on clinical olfactory tests. METHODS: Twenty-five patients with posttraumatic olfactory dysfunction were examined by means of olfactory testing, endoscopy, and MR imaging. MR surface-coil scans through the olfactory bulbs and tracts and head-coil scans of the temporal lobes were evaluated. Quantitative and qualitative gradings of damage to the olfactory bulbs, tracts, subfrontal region, hippocampus, and temporal lobes were compared with results on tests of odor identification, detection, memory, and discrimination. RESULTS: Twelve patients were anosmic, eight had severe impairment, and five were mildly impaired. Injuries to the olfactory bulbs and tracts (88% of patients), subfrontal region (60%), and temporal lobes (32%) were found, but these did not correlate well with individual olfactory test scores. Volumetric analysis showed that patients without smell function had greater volume loss in olfactory bulbs and tracts than did those posttraumatic patients who retained some sense of smell. Qualitative and quantitative assessments of damage showed few significant correlations with olfactory tests, probably because of multifocal injuries, primary olfactory nerve damage, and the constraints of a small sample size on the detection of clinically significant differences. CONCLUSION: MR imaging shows abnormalities in patients with posttraumatic olfactory dysfunction at a very high rate (88%), predominantly in the olfactory bulbs and tracts and the inferior frontal lobes. Department of Radiology, University of Pennsylvania Medical Center, Philadelphia 19104, USA.

[Jonh]

This is all very interesting. I have been in contact with someone who has Posttraumatic olfactory dysfunction. They have asked me if in theory umbilical cord or fetal stem cells could improve this condition. If so, would intrathecal injections reach the nerve or would the stem cells need to be directly injected near the olfactory nerve?

Any thoughts on this would be appreciated.

Thank you.

[Wise Young]

This is all very interesting. I have been in contact with someone who has Posttraumatic olfactory dysfunction. They have asked me if in theory umbilical cord or fetal stem cells could improve this condition. If so, would intrathecal injections reach the nerve or would the stem cells need to be directly injected near the olfactory nerve?

Any thoughts on this would be appreciated.

Thank you.

Jonh, the condition of post-traumatic olfactory dysfunction, I believe, stems from the shearing of the olfactory nerve where it enters the cranial cavity, through the cribiform plate. This opening is perforated with tiny holes through which the olfactory nerves pass to get to the olfactory bulb. After the injury, there is often fibrous scarring of the cribiform plate and inabiity of the olfactory nerve to regenerate. It seems to me that the answer to this condition is some kind of surgical procedure that would allow the olfactory nerve (which usually can regenerate) to regrow back to the olfactory bulb. One possibility may be to put an artificial conduit from the nasal mucosa to the olfactory bulb.

Wise.

[brainhelp]

Thank you very much for all this info. It's very helpful. Keep the good work.

Cheers,

Michelle